Dibutyltindichloride
| 1. NAME |
| 1.1 Substance |
| 1.2 Group |
| 1.3 Synonyms |
| 1.4 Identification numbers |
| 1.4.1 CAS number |
| 1.4.2 Other numbers |
| 1.5 Main brand names, main trade names |
| 1.6 Main manufacturers, main importers |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.3 Diagnosis |
| 2.4 First-aid measures and management principles symptomatic treatment. |
| 3. PHYSICO-CHEMICAL PROPERTIES |
| 3.1 Origin of the substance |
| 3.2 Chemical structure |
| 3.3 Physical properties |
| 3.3.1 Colour |
| 3.3.2 State/Form |
| 3.3.3 Description |
| 3.4 Hazardous characteristics |
| 4. USES |
| 4.1 Uses |
| 4.1.1. Uses |
| 4.2 High risk circumstance of poisoning |
| 4.3 Occupationally exposed populations |
| 5. ROUTES OF EXPOSURE |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Other |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological half-life by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination by route of exposure |
| 7. TOXICOLOGY |
| 7.1 Mode of Action |
| 7.2 Toxicity |
| 7.2.1 Human data |
| 7.2.1.1 Adults |
| 7.2.1.2 Children |
| 7.2.2 Relevant animal data |
| 7.2.3 Relevant in vitro data |
| 7.2.4 Workplace standards |
| 7.2.5 Acceptable daily intake (ADI) |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS |
| 8.1 Material sampling plan |
| 8.1.1 Sampling and specimen collection |
| 8.1.1.1 Toxicological analyses |
| 8.1.1.2 Biomedical analyses |
| 8.1.1.3 Arterial blood gas analysis |
| 8.1.1.4 Haematological analyses |
| 8.1.1.5 Other (unspecified) analyses |
| 8.1.2 Storage of laboratory samples and specimens |
| 8.1.2.1 Toxicological analyses |
| 8.1.2.2 Biomedical analyses |
| 8.1.2.3 Arterial blood gas analysis |
| 8.1.2.4 Haematological analyses |
| 8.1.2.5 Other (unspecified) analyses |
| 8.1.3 Transport of laboratory samples and specimens |
| 8.1.3.1 Toxicological analyses |
| 8.1.3.2 Biomedical analyses |
| 8.1.3.3 Arterial blood gas analysis |
| 8.1.3.4 Haematological analyses |
| 8.1.3.5 Other (unspecified) analyses |
| 8.2 Toxicological Analyses and Their Interpretation |
| 8.2.1 Tests on toxic ingredient(s) of material |
| 8.2.1.1 Simple Qualitative Test(s) |
| 8.2.1.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.1.3 Simple Quantitative Method(s) |
| 8.2.1.4 Advanced Quantitative Method(s) |
| 8.2.2 Tests for biological specimens |
| 8.2.2.1 Simple Qualitative Test(s) |
| 8.2.2.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.2.3 Simple Quantitative Method(s) |
| 8.2.2.4 Advanced Quantitative Method(s) |
| 8.2.2.5 Other Dedicated Method(s) |
| 8.2.3 Interpretation of toxicological analyses |
| 8.3 Biomedical investigations and their interpretation |
| 8.3.1 Biochemical analysis |
| 8.3.1.1 Blood, plasma or serum |
| 8.3.1.2 Urine |
| 8.3.1.3 Other fluids |
| 8.3.2 Arterial blood gas analyses |
| 8.3.3 Haematological analyses |
| 8.3.4 Interpretation of biomedical investigations |
| 8.4 Other biomedical (diagnostic) investigations and their interpretation |
| 8.5 Overall Interpretation of all toxicological analyses and toxicological investigations |
| 8.5.1 Sample collection |
| 8.5.2 Biomedical analysis |
| 8.5.3 Toxicological analysis |
| 8.5.4 Other investigations |
| 8.6 References |
| 9. CLINICAL EFFECTS |
| 9.1 Acute poisoning |
| 9.1.1 Ingestion |
| 9.1.2 Inhalation |
| 9.1.3 Skin exposure |
| 9.1.4 Eye contact |
| 9.1.5 Parenteral exposure |
| 9.1.6 Other |
| 9.2 Chronic poisoning |
| 9.2.1 Ingestion |
| 9.2.2 Inhalation |
| 9.2.3 Skin exposure |
| 9.2.4 Eye contact |
| 9.2.5 Parenteral exposure |
| 9.2.6 Other |
| 9.3 Course, prognosis, cause of death |
| 9.4 Systematic description of clinical effects |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurological |
| 9.4.3.1 Central Nervous System (CNS) |
| 9.4.3.2 Peripheral nervous system |
| 9.4.3.3 AutoNomic nervous system |
| 9.4.3.4 Skeletal and smooth muscle |
| 9.4.4 Gastrointestinal |
| 9.4.5 Hepatic |
| 9.4.6 Urinary |
| 9.4.6.1 Renal |
| 9.4.6.2 Other |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ears, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid-base disturbances |
| 9.4.12.2 Fluid and electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Others |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Life supportive procedures and symptomatic treatment |
| 10.3 Decontamination |
| 10.4 Enhanced elimination |
| 10.5 Antidote treatment |
| 10.5.1 Adults |
| 10.5.2 Children |
| 10.6 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 12. ADDITIONAL INFORMATION |
| 12.1 Specific preventive measures |
| 12.2 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES) |
DIBUTYLTINDICHLORIDE
International Programme on Chemical Safety
Poisons Information Monograph 586
Chemical
1. NAME
1.1 Substance
dibutyltindichloride
1.2 Group
organotin compounds
1.3 Synonyms
di-n-butyltin dichloride,
dibutyldichlorostannane,
dibutyldichlorotin,
dibutyltin chloride,
dichlorodibutylstannane,
dichlorodibutyltin,
1.4 Identification numbers
1.4.1 CAS number
683-18-1
1.4.2 Other numbers
1.5 Main brand names, main trade names
1.6 Main manufacturers, main importers
2. SUMMARY
2.1 Main risks and target organs
After skin and eye contact, local irritation and
inflammation will occur after 1-8 hours, without workers
being aware of it at the moment of exposure.In vitro and in
vivo experiments immunosuppressive properties were
observed
Summary of clinical effects
Local skin and eye irritation and inflamation my occur after
a latent period of 1-8 hours.Lymphocytoxic and
immunosupressive properties are only observed in in vitro and
in vivo animal experiments up to now.
2.3 Diagnosis
irritation of skin and eyes.
2.4 First-aid measures and management principles
symptomatic treatment.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
The reaction between HCl and the stabilizer dibutyltin
most probably produces dibutyltin dichloride (Boyer,
1989)
3.2 Chemical structure
(C4H9)2SnCl2
3.3 Physical properties
3.3.1 Colour
3.3.2 State/Form
3.3.3 Description
Molecular weight.: 303.83
Crystalline form: white needles
Index of refraction: 1.499
Specific gravity:1.36
Melting point: 142°C
Boiling point: decomposes 113.6°C
Solubility:
- decomposes in cold water
- decomposes in hot water
- soluble in ether. benzene, and alcohol.(Weast &
Selby, 1967)
3.4 Hazardous characteristics
No data available.
4. USES
4.1 Uses
4.1.1. Uses
<4.1.1.>Description
The presence of 0.5-3% of a dibutyltin stabilizer
prevents the degradation of plastics by combining with
the HCl liberated from the polymer during
manufacturing processes which require high
temperatures (Frey et al.1964).
4.2 High risk circumstance of poisoning
No data available.
4.3 Occupationally exposed populations
Process workers in contact with butytin compounds.
5. ROUTES OF EXPOSURE
5.1 Oral
In animal experiments
5.2 Inhalation
No data vailble.
5.3 Dermal
Occupationally and in volunteers
5.4 Eye
Irritation of the eye
5.5 Parenteral
No data available
5.6 Other
No data available
6. KINETICS
6.1 Absorption by route of exposure
No data available
6.2 Distribution by route of exposure
After dibutyltin intravenously the highest concentration
was found in the liver with a small amount in the kidneys
(Barnes & Magee, 1958)
6.3 Biological half-life by route of exposure
No data available
6.4 Metabolism
No data available
6.5 Elimination by route of exposure
No data available
7. TOXICOLOGY
7.1 Mode of Action
The ations of homologous series of di-substituted
orgaNotin compounds from dimethyl to dioctyltin are
inhibiting of mitochondrial respiration by preventing the
oxidation of keto- acids, presumaly via the inhibition of
alpha-keto oxidase activity, leading to the accumulation of
pyruvate (Aldridge, 1976; Piver 1973).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
No data available
7.2.1.2 Children
No data available
7.2.2 Relevant animal data
LD50 rat orally in oil solution 100 mg/kg
(Klimmer 1969)
7.2.3 Relevant in vitro data
In vitro dibutyltin dichloride is extremely
cytotoxic. Blast transformation of human as well as
rat thymocytes was already inhibited at concentrations
as low as 0.02 microgram dibutyltindichloride ml
medium (Seinen et al., 1979).
7.2.4 Workplace standards
Maximum allowable concentration value
(calculated as tin) has been issued for organotin
compounds at 0.1 mg/m3 (Zuckerman et al 1978). To
avoid local irritation momentary (5 minutes) values
should not exceed 0.2 mg/m3 (MAK 1987).
7.2.5 Acceptable daily intake (ADI)
Once incorporated into final consumer products,
the potential for tin compound is not likely to pose a
major human health hazard. The daily intake should
not exceed 15 ng (normally 1-5 ng (Merian
1991).
7.3 Carcinogenicity
No data available.
7.4 Teratogenicity
No data available.
7.5 Mutagenicity
No data available.
7.6 Interactions
No data available.
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
Small quantities of dialkyltin are extractable
from PVC bottles into biological fluids (Piver, 1973).
The Food and Drug Administration has permitted the use
a.o. dioctyl maleate, dioctyl-S,S'-bis (isooctyl
mercapto acetate) at levels not to exceed 3% in
resin,to stabilize plastic bottles and films which
contact food. These long-chained organotin compounds
were though to be less toxic than the dibutyltin
derivates because they are relatively insoluble in
bodt fluids and poorly absorbed from the gastro
intestinal tract (Barnes & Stoner 1958).
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and
their interpretation
8.5 Overall Interpretation of all toxicological analyses and
toxicological investigations
8.5.1 Sample collection
8.5.2 Biomedical analysis
8.5.3 Toxicological analysis
8.5.4 Other investigations
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
No data available
9.1.2 Inhalation
Irritation of the respiratory tract.
9.1.3 Skin exposure
No visible changes occured for 1-8 hours after
exposure, thereafter irritation and on the second day
the development of sterile inflamation. After one
week the lesions had practically disappeared.
9.1.4 Eye contact
Irritation of the eyes.
9.1.5 Parenteral exposure
No data available
9.1.6 Other
No data available
9.2 Chronic poisoning
9.2.1 Ingestion
No data available
9.2.2 Inhalation
Irritation of the respiratory tract
9.2.3 Skin exposure
Irritation and inflammation of the skin
9.2.4 Eye contact
No data available
9.2.5 Parenteral exposure
No data available
9.2.6 Other
No data available
9.3 Course, prognosis, cause of death
No data available.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
No data available.
9.4.2 Respiratory
Pulmonary oedema occured in rats after a single
i.v.injection of dibutyltin dichloride 10 mg/kg
(Barnes & Stoner 1958).
9.4.3 Neurological
9.4.3.1 Central Nervous System (CNS)
No data available
9.4.3.2 Peripheral nervous system
No data available.
9.4.3.3 AutoNomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
No data available.
9.4.4 Gastrointestinal
No data availabe.
9.4.5 Hepatic
Alkyltin-induced damage to the bile duct is
specific to animal species which, unlike man, have
common bile duct systems (Kimbrough 1976). A single
dose of dibutyltin dichloride of 30 mg/kg by gavage
produced distal bile duct necrosis and papillary
regeneration proliferation in hamsters within 7 days
after administration. In contrast rabbits, guinea
pigs, hens and cats, all of which have separate bile
ducts and pancreatic duct systems, do not exhibit
bile duct injury after dibutyltin dichloride treatment
(Barnes & Stoner, 1959; Barnes & Magee,
1958).
9.4.6 Urinary
9.4.6.1 Renal
No data available.
9.4.6.2 Other
No data available.
9.4.7 Endocrine and reproductive systems
No data available.
9.4.8 Dermatological
After application, no visible changes occured
for 2h to 3h, although a swelling of the mouth of the
hair follicles was noticeble. The follicular
inflammation progressed during the following 8h with
only slight visible irritation of the skin between
the openings of the follicles. On the second day,
sterile pustules developed over the follicular
openings, but remained small during the next 3 to 4
days. After one week, the lesions had practically
disapeared (Lyle, 1958). Dibutyltin dichloride at 335
nmol/cm2 produced epidermal necrosis and dermal
inflammation within 24 hours.[Tributyltin chloride
produced the same effect already at 23
nmol/cm2].
9.4.9 Eye, ears, nose, throat: local effects
Lacrimation and severe suffusion of the
conjunctivae appeared within a few minutes and
persisted for 4 days. Immediate lavage of the eye
did not prevent development of the signs (Lyle,
1958).
9.4.10 Haematological
Since dibutyltin compounds induce
immunosupression selectively, T-lymphocytes are
predominantly involved (Seinen et al., 1979).
9.4.11 Immunological
Dibutyltin dichloride is lymphocytotoxic and
immunosuppressive. Dietary levels of dibutyltin
dichloride as low as 20 ppm produced thymus atrophy in
rats within 2 weeks (Seinen et al., 1977a). Immune
responses were diminished in weaning rats fed 50-150
ppm dibutyltin dichloride or 150 ppm dioctyl tin
dichloride in the diet for 6 weeks, corresponding to
the decrease in the weight and number of cells of the
thymus (Seinen et al., 1977b). The functional
disturbance was manifested by an inhibition in
cell-reaction to tuberculin, skin allograft rejection,
graft-vs-host reactivity and cells, and peripheral
lymphe-nodes. The E-rossette formation was inhibited
at very low levels (Seinen et al., 1977b; 1979a;
1979b).
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
No data available.
9.4.12.2 Fluid and electrolyte disturbances
No data availble.
9.4.12.3 Others
No data available.
9.4.13 Allergic reactions
No data availble.
9.4.14 Other clinical effects
No data availabe.
9.4.15 Special risks
No data available.
9.5 Others
No data available.
9.6 Summary
10. MANAGEMENT
10.1 General principles
Decontamination of the exposed skin and clothes.
10.2 Life supportive procedures and symptomatic treatment
Not applicable.
10.3 Decontamination
Skin contact with the colorless dibutyltin chlorides
does not immediately give any symptom or sign. Although
prevention of later effects may not be effective, washing
with water and soap is indicated. Clothes that have been
moistened by vapour or liquid compounds must be immediately
taken off.
10.4 Enhanced elimination
No data available.
10.5 Antidote treatment
10.5.1 Adults
2.3.dimercapto propanol (BAL) prevents the
accumulation of alpha-keto acids produced by the
dialkyltins in animal experiments. BAL proved to be
an effective antidote (Stoner at al., 1955).
10.5.2 Children
No data availble.
10.6 Management discussion
2.3 dimercapto propanol (BAL) prevents the accumulation
of alpha-keto acids produced by the dialkyltins in animal
experiments. BAL proved to be an effective antidote (Stoner
et al., 1955).
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
A single dermal application of undiluted dibutyltin
diacetate,dibutyltin dilaurate,dibutyltin oxide, dibutyltin
maleate on the back of the hands of volunteers was not
irritating. Incontrast,exposed areas of the skin reddened
within 8 hours after a single application of dibutyltin
dichloride. This effect was accompanied by follicular
inflammation and pruritus (Lyle, 1958).
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
No data available
12.2 Other
No data available
13. REFERENCES
Aldridge WN (1976) The influence of organotin compounds on
mitochondrial functions. In: Zuckerman JJ,ed Organotin
compounds:New chemistry and applications,Washington DC American
Chemical Society, pp.186-196.
Barnes JM, Magee PN (1958) The biliary and hepatic lesion produced
experimentally by dibutyltin salts. J Pathol Bacteriol
75:267-279.
Barnes JM, Stoner HB (1959) The toxicology of tin compounds.
Pharmacol Rev 11:211-231.
Boyer IJ (1989) Toxicity of dibutyltin,tributyltin and other
organotin compounds to humans and to experimental animals.
Toxicology 55:253-298.
Frey AH, Horst RW, Paliobagis MA (1964) The chemistry of
poly(vinyl)chloride stabilization.J Polym Sci 2:1765
Kimbrough RD (1976) Toxicity and health effects of selected
organotin compounds; A review. Environ Health Perspect
14:51-56.
Klimmer OR (1969) [The application of organotin compounds reviewed
by the experimental toxicologist] Arzneim Forsch 19:934-939 (in
German).
Lyle W (1958) Lesions of the skin in process workers caused by
contact with butyltin compounds. Br J Ind Med 15:193-196.
MAK (1987) Maximum Concetrations at the Workplace,Report No.XXIII
DFG. VCH Verlagsgesellschaft,Weinheim-Basel-Cambrige-New
York.
Merian E ed. (1991) Metals and Their Compounds in the Environment
VCH Verlagsgesellschaft,Weinheim-Basel-Cambridge-New York.
Piver WT (1973) Organotin compounds: Industrial applications and
biological investigation. Environ Health Perspect 4:61-79.
Seinen W, Vos JG, van Spanje I, Snoek M, Hooykaas H (1977a)
Toxicity of organotin compounds II Comparative in vivo and in
vitro studies with various organotin and organolead compounds in
different animal species with special emphasis on lymphocyte
cytotoxicity. Toxicol Appl Pharmacol 42:179-212.
Seinen W, Vos JG, van Krieken R, Penninks A, Brands R, Hooykaas H
(1977b) Toxicity of organotin compounds III Supression of
thymus-dependent immunity in rats by di-n-butyltin dichloride and
di-n-octyltin dichloride. Toxicol Appl Pharmacol 42:213-224.
Seinen W, Penninks A (1979a) Immune supression as a consequence of
a selective cytotoxic activity of certain organometallic compounds
in thymus and thymus-dependent lymphocytes. Ann NY Acad Sci
320:499-517
Seinen W, Vos JG, Brands R, Hooykaas H (1979b) Lymphocytotoxicity
and immunosuppression by organotin compounds: Suppression of GVH
-activity; blast transformation and E-rosette formation by
di-n-butyltin dichloride and di-n-octyltin dichloride.
Immunopharmacology 1:343-355.
Stoner HB, Barnes JM, Duff JI (1955) Studies on the toxicity of
alkyltin compounds. Br J Pharmacol 10:16-25.
Weast RC, Selby SM (1967) Handbook of Chemistry and Physics 48ed.
pg C-677, The Chemical Rubber Co. Cleveland, Ohio.
Zuckermann JJ, Reisdorf RP, Ellis III HV, Wilkinson RR (1978) ACS
Symp.Ser.82:388-424.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: Prof.Dr.A.N.P.van Heijst
Baarnse weg 42 A
3735 MJ Bosch en Duin
The Netherlands.
Telephone (30)287178
Date: August 1993.
Peer Review: PIM Peer Review Group in Cardiff: Besbelli,
O.Kasilo, L.Lefebre, J.Szajewski, W.Temple,
A.N.P.van Heijst.
Date: February 1994