Registration Dossier

Administrative data

Description of key information

Oral:
Sanders, A 2010 ACUTE ORAL TOXICITY IN THE RAT - FIXED DOSE METHOD Testing Laboratory: Harlan Laboratories Limited, Shardlow Business Park, Shardlow, Derbyshire, DE72 2GD, UK. Owner company: Chemtura Corporation, 199 Benson Road, Middlebury, CONNECTICUT 06749, UNITED STATES OF AMERICA. Report date: 3103/0068
The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (OECD 420).
Dermal:
Both available acute dermal toxicity studies have included 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, however this is reduced to 2 as the study is being used for read-across purposes. The study was performed to the guideline OECD 402 and conducted in line with 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 as the key value.

Key value for chemical safety assessment

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
777 mg/kg bw

Additional information

ORAL

Key value for chemical safety assessment:

LD50 (oral): >2000 mg/kg bw

The key study (Sanders, 2010) was performed to assess the acute oral toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

OECD Guidelines for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (2001)

Method B1 bis Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

A reliability score of 1 was assign according to Klimisch, 1997 as the study was conducted to recognised guidelines and GLP.

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of the undiluted test material 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.

 

DERMAL

Read across from DBT-2EHMA (CAS: 10584-98-2) has been used for this endpoint as this is considered the most structurally similar organotin substance with regards to diisotridecyl 3,3'-[(dibutylstannylene)bis(thio)]dipropionate.

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)

Justification for classification or non-classification

The LD50 values for acute oral toxicity and acute dermal toxicity are > 2000 mg/kg bw and 777 mg/kg bw respectively, the classification triggered under 67/548/EEC and EC Regulation 1272/2008 are presented as follows: - 67/548/EEC: R21 - Harmful in contact with skin; - EC Regulation 1272/2008: Acute toxicity: Dermal, Category 3: H311 Toxic in contact with skin.