Registration Dossier

Administrative data

Description of key information

ORAL
The key study, reports the lowest LD50 and therefore gives the worst case scenario, also, the test material composition contains a higher proportion soybean oil than monobutyltintris(2-ethylhexylthioglycolate) compared to the other 3 studies by the same laboratory. 7 further studies were provided in support:
Sarasin, G. (1980) Acute Oral LD50 in the Rat of TK 10701. Testing Laboratory: CIBA-GEIGY Limited, Basle, Switzerland. Owner company: Crompton GmbH, Polymerchemilkalien, Postfach 1620, D-59180, Bergkamen. Report No.: 801408. Report date: 1980-10-20.
The study was performed to OECD 401, reported to a good standard and assigned a reliability score of 2. The LD50 was reported as 369 mg/kg bw.
DERMAL
The studies are presented as a weight of evidence.
Arcelin. G (2001) Mark 17M: Acute Dermal Toxicity Study in Rats. Testing Laboratory: RCC Ltd, Toxicology Division, Wölferstrasse 4, CH-4414, Füllinsdorf Switzerland. Owner company: Crompton Vinyl Additives GmbH, Chemiestrasse 22, D-68623 Lampertheim, Germany. Report No.: 785687. Report date: 2001-06-21.
Sarasin G (1981) Acute Dermal LD50 in the Rat of TK 10'701. Testing Laboratory: CIBA-GEIGY Limited, Basle, Switzerland. Owner company: Plastics and Additives Division, CIBA-GEIGY MARIENBERG GMBH, 6140 Marienberg Post Bensheim. Report No.: 810905. Report date: 1981-09-17
Arcelin G (2001) was assigned a reliability score of 1. The study was performed to OECD 402 and to GLP. The second study Sarasin G (1981) was also performed to a method equivalent to OECD 402 and assigned a reliability score of 2.
The lowest LD50 was selected, 777 mg/kg bw
INHALATION
Stevens J (1980) Report on Acute Aerosol Inhalation Toxicity in the Rat of TK-12824 Testing laboratory: CIBA-GEIGY Limited, Basle, Switzerland Owner company: Plastic and Additives Division Report No.: 801474. Report date: 1980-10-30
The study was performed to a good standard and assigned a reliability score of 2. The LC50 was 941 (758-1283) mg/m^3.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
396 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
941 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
777 mg/kg bw

Additional information

ORAL

Sarasin, G. (1980) was provided as the key study for this data requirement. The study was performed to a method equivalent to OECD 402 and reported to a good standard. The test material utilised in the study (TK 10701)contained 61.8% of the substance of interest, with the lowest content of monobutyltintris(2-ethylhexylthioglycolate) (25.3 %). The study also provided the lowest available LD50, the study was therefore selected as the key study as it produced the worst case scenario. In the study,groups of male and female 7 - 8 week old rats were given a single oral dose of TK 10701 in propylene glycol. Doses of  100, 200, 1000 and 2000 mg/kg bw and observed for 14 days. The acute oral LD50 of TK 10701 in rats of both sexes observed over a period of 14 days is 396 (174 - 180) mg/kg.

 

The further 7 available studies for acute oral toxicity are summarised below:

 

Reference: Dr Sarasin. P.G. (1981)

Reliability and rationale: 2 (reliable with restrictions) Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Results: In an acute oral toxicity study (811185), 7 - 8 week old male and female Tif: RAIf(SPF) rats weighing 165 - 188 g were given a single dose of TK 11'638 via oral intubation. The acute oral LD50 of TK 11'638 in rats of both sexes observed over a period of 14 days is 758 mg/kg. The test material is therefore slightly toxic to the rat by this route of administration.

 

Reference: Sarasin, G. (1982)

Reliability and rationale: 2 (reliable with restrictions) Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Results: In an acute oral toxicity study (811865), 7 - 8 week old male and female Tif: RAIf(SPF), F3-crosses of RII 1/TifxR11 2/Tif rats weighing 160 - 197 g were given a single dose of TK 12079 via oral intubation. The LD50 was determined as 615 mg/kg bw with 95 % CL of 132 - 1248 mg/kg bw and therefore has slight acute oral toxicity to the rat.

 

Reference: Schoch, M. (1981)

Reliability and rationale: 2 (reliable with restrictions) Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Results: In an acute oral toxicity study (811865), 7 - 8 week old male and female Tif: RAIf(SPS) P3-hybrid of RII 1/Tif x RII 2/Tif weighing 169 - 222 g were given a single dose of TK 11638/1 via oral intubation. The LD50 was determined as 4439 mg/kg bw and does therefore not need to be classified.

 

Reference: Figge, K. and Koch, J. (1973)

Reliability and rationale: 4 (not assignable) Data taken from Migration study with only limited data in relation to the Acute oral toxicity test.

Results: The LD50 of the test substance to rats is 510 mg/kg body weight.

 

Reference: Klimmer, O.R. (1969)

Reliability and rationale: 4 (not assignable) No English version of the report is available. Only basic details of testing conducted.

Results: The actute oral LD50 of male rats in 510 mg/kg body weight. This is classified as harmful.

 

Reference: Mesch, K.A. and Kugele, T.G. (1992)

Reliability and rationale: 4 (not assignable) Secondary information taken from publication with little information about animals or testing procedure.

Results: The acute oral LD50 of rats in 510 mg/kg body weight. This is classified as harmful.

 

Reference: Smith, P.J. (1978)

Reliability and rationale: 4 (not assignable) Secondary information taken from publication with little information about animals or testing procedure.

Results: The acute oral LD50 of rats in 510 mg/kg body weight. This is classified as harmful.

 

DERMAL

Two studies were available for the assessment of the acute dermal toxicity endpoint. The LD50 value selected for assessment was that from the Sarasin (1981) study. The study was performed to a good scientific standard, with a good level of reporting. The study was therefore assigned a reliability score of 2 in line with the criteria in Klimisch (1997). The Arcelin (2001) study was assigned a reliability score of 1. The study was performed in compliance with GLP and to the OECD guideline 402, however it was considered preferable to take the worst case value from the Sarasin study. Furthermore, the test material in the Sarasin study contained a higher percentage of the substance in question.

 

In the Arcelin study according to OECD test guideline 402, groups of 9 week old male and 10 - 11 week old female rats were dermally exposed to Mark 17 M for 24 hours at doses of 1000 and 2000 mg/kg bw. Animals dosed with 1000 mg/kg bw were then observed for 14 days. All animals treated with 2000 mg/kg were killed for ethical reasons on day 8 due to severe signs of irritation observed. The LD50 result for these test animals are classified as inconclusive (>1000 mg/kg).

 

In Sarasin, groups of 7-8 week old male and female rats were dermally exposed to TK 10'701 for 24 hours at doses of 250, 500, 1000 and 2000 mg/kg bw.  Animals were then observed for 14 days.

LD50 = 777 mg/kg bw (95% C.I. of 575 and 1052 mg/kg)

INHALATION

Stevens J (1980) was provided as the key study for the endpoint, the GLP status of the study is unknown, however the study was performed in a similar or equivalent way to the OECD 403 Guideline and there was sufficient detail in the reporting of the methods and the results. The study was performed in line with good scientific principles, therefore the study was assigned a reliability score of 2 and considered adequate for assessment.

Justification for classification or non-classification

The LD50 values for acute oral toxicity, acute dermal toxicity and acute inhalation toxicity are 396 mg/kg bw, 777 mg/kg bw and 941 mg/m3 (0.941 mg/L) respectively, the classification triggered under 67/548/EEC and EC Regulation 1272/2008 are presented as follows: 67/548/EEC: R22 - Harmful if swallowed, R21 - Harmful in contact with skin and R23 Toxic by inhalation; EC Regulation 1272/2008: Acute toxicity: Oral, Category 4: H302 Harmful if swallowed, Acute toxicity: Dermal, Category 3: H311: Toxic in contact with skin and Acute toxicity: Inhalation Category 3: H331 Toxic if Inhaled.