Registration Dossier

Administrative data

Description of key information

Oral:
The acute oral LD50 of TK 10708 in rats of both sexes observed over 14 days is 2071 mg/kg in a study conducted using a method which is considered similar to that in OECD Guideline 401. The test material is considered to be slightly toxic to the rat by this route of administration.
Dermal:
The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat observed over 14 days was determined to be greater than 2000 mg/kg bodyweight (in an GLP study conducted to OECD 402). Irritation was observed, and one female animal exhibited some symptoms of toxicity, however the test material did not meet the criteria for classification as acutely toxic via the dermal route.
Inhalation:
A waiver has been submitted to address the acute toxicity: inhalation endpoint on the basis of lack of exposure

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 071 mg/kg bw

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
The study was performed between 19 May 2010 and 02 June 2010.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Giudeline study conducted to GLP.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Oxon, UK.
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: at least 200g. The weight variation did not exceed ± 20% of the mean weight for each sex.
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet /water(e.g. ad libitum): Free access to mains drinking water and food (2014 Teklad Global Rodent diet supplied by Harlan Laboratories U.K. Ltd., Oxon, UK) was allowed throughout the study.
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
TEST SITE
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material.
- Time after start of exposure: 24 hours

Duration of exposure:
24 hours
Doses:
Using available information on the toxicity of the test material, a group of five male and five female rats was treated with the test material at a dose level of 2000 mg/kg.
No. of animals per sex per dose:
five male and five female rats
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Data evaluations included the relationship, if any, between the exposure of the animal to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All males showed expected gains in bodyweight over the study period. Bodyweight loss was noted in all females during the first week with expected gain in bodyweight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Well-defined erythema and very slight oedema were noted at the test sites of all animals. Other dermal reactions noted were haemorrhage of dermal capillaries, loss of skin elasticity and flexibility, small superficial scattered scabs, hardened light brown coloured scab, scab lifting to reveal glossy skin, scab undulating, scab cracking and glossy skin. Adverse dermal reactions prevented accurate evaluation of erythema and oedema at the test sites of all animals during the study.

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

The study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

¿ OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)

¿ Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008

A group of ten animals (five males and five females) was given a single, 24 hour, semi occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths or signs of systemic toxicity.

Well-defined erythema and very slight oedema were noted at the test sites of all animals. Other dermal reactions noted were haemorrhage of dermal capillaries, loss of skin elasticity and flexibility, small superficial scattered scabs, hardened light brown coloured scab, scab lifting to reveal glossy skin, scab undulating, scab cracking and glossy skin.

All males showed expected gains in bodyweight over the study period. Bodyweight loss was noted in all females during the first week with expected gain in bodyweight during the second week.

No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

The following studies are available to address the acute oral toxicity endpoint:

Sarasin, G. (1981). Report on Acute Oral LD50 in the Rat of TK 10708. Testing laboratory: Ciba-Geigy Limited. Report no.: Project No. 811182. Owner company: Plastics and Additives Division, CIBA-GEIGY Ltd. Report date: 1981-11-13.

Schafer, E. W. and Bowles, W. A. (1985). Acute oral toxicity and repellancy of 933 chemicals to house and deer mice. Archives of Environmental Contamination and Toxicology. 14:111-129. Testing laboratory: U. S. Department of Interior - Fish and Wildlife Service.

Result: These authors reported an ALD (approximate lethal dose) for dibutyltin dilaurate of 710 mg/kg in wild caught deer mice.

Walterson, E., Sangfors, O. and Landner, L. (1994). A collection of results of toxicological evaluation of substances and products. Mono- and Di-Substituted Organotins Used as Plastic Additives. Vol 1 Environmental Hazard Assessment, Swedish National Chemicals Inspectorate, Solna, Sweden. Report no.: KEMI Report No. 11/94.

Result: The acute oral LD50 value reported for rats as between 33 and 300 mg Sn/kg body weight in the KEMI Report.

Nordenhall, K., Dock, L. and Vahter, M. (1994a). Dibutyltin dilaurate. Toxicity Profile. Mono- and Di-Substituted Organotins Used as Plastic Additives. Vol 2 Health Hazard Identification, Swedish National Chemicals Inspectorate, Solna, Sweden. Report no.: KEMI Report No. 11/94.

Nordenhall, K., Dock, L. and Vahter, M. (1994b). Dibutyltin dilaurate. Mono- and Di-Substituted Organotins Used as Plastic Additives. Volume 2 Health Hazard Identification. Swedish National Chemicals Inspectorate, Solna, Sweden. Report no.: KEMI Report No. 11/94.

Sarasin (1981) and Schafer and Bowles (1985) have been allocated a Klimisch score of 2; the other three references are secondary literature and have been allocated a Klimisch score of 4. Sarasin is a study report, whereas Schafer and Bowles is a scientific paper, and so Sarasin, 1981 has been allocated as the key study.

A waiver has been submitted to address the acute toxicity: inhalation endpoint on the basis of lack of exposure.

Acute toxicity via the dermal route was addressed with the study Sanders A (2010). The study was conducted in accordance with the OECD guideline 402 (also EU Method B.3). The study was performed in compliance with GLP. The study was assigned a reliability score of 1 and considered adequate for assessment as a stand alone study. The study was designated as the key study for the acute toxicity endpoint via the dermal route.

Justification for classification or non-classification

In accordance with the directive 67/548/EEC and the regulation (EC) No 1272/2008, the substance does not meet the criteria for classification as acutely toxic based on read across to structurally similar substances.