Dibutyltin oxide

Endpoint summary

Description of key information

The following data were submitted to address the endpoint acute toxicity:

ORAL

Key Study: Bioneeds (2019)

Amulya TS (2019) Acute Oral Toxicity Study of Dibutyltin Oxide, FASCAT® 4201 in Sprague Dawley Rats. Testing Laboratory: BIONEEDS INDIA PRIVATE LIMITED, DEVARAHOSAHALLY, SOMPURA HOBLI, NELAMANGALA TALUK, BANGALORE RURAL DISTRICT, PIN - 562 111, KARNATAKA, INDIA. Owner company: PMC ORGANOMETALLIX INC., 2316 HIGHLAND AVE CARROLLTON, KY 41008, USA. Project number: BIO-ATX 051. Report date: 2019-02-14.

 

Supporting Studies:

Thevenaz, P.H. (1983). TK13019.  Acute Oral  LD50 in the Rat. Testing Laboratory: CIBA-GEIGY, Ltd., Sisseln facility, CH-4332 Stein, Switzerland. Owner company: Plastics and Additives Division, Ciba-Geigy Limited. Report No.: GU Project Number 821571. Report date: 1983-02-24

M&T Chemicals, Inc. (1977) Acute oral toxicity study in rats -  Thermolite 15, JCRDY-611K, 4201. Testing Laboratory: Bio/Dynamics, Inc., Toxicological Resources Unit. Owner company: M&T Chemicals, Inc. Company study No.: 4542-77. Report date: 1978-01-04.

Schering AG, Experimentelle Toxikologie (1971) Systemische  Verträglichkeitsprüfung an Ratten bei einmaliger p.o. Verabreichung  (DL50). Owner company: Schering AG, Experimentelle Toxikologie. Company study No.: 1971-01-04.

Klimmer, O.R. von. (1969) IN  Toxicological Data on Organotin Compounds.  Smith, P.J.  International  Tin Research Institute.  Publication 538.

Auletta CS (1980) Acute Oral Toxicity Study in Rats. Testing Laboratory: Bio/dynamics Inc. Owner company: M&T Chemical Inc., Rahway, New Jersey, USA. Project number: 6056-79 Report date: 1980-06-30

Auletta CS (1980) Acute Oral Toxicity Study in Rats. Testing Laboratory: Bio/dynamics Inc. Owner company: M&T Chemical Inc., Rahway, New Jersey, USA. Project number: 6055-79. Report date: 1980-06-05

Ciba-Geigy Ltd. (1972) Acute oral LD50 of TK 11285 in the rat. Owner company: CIBA-GEIGY, Ltd. Company study No.: Project  No. Siss 2501. Report date: 1972-12-14.

DERMAL

A Sanders (2010) ACUTE DERMAL TOXICITY (LIMIT TEST) IN THE RAT. Testing laboratory: Harlan Laboratories Limited, Shardlow Business Park, Shardlow, Derbyshire, DE72 2GD, UK. Owner company: Organo Tin REACH Consortium, c/o ReachCentrum, Avenue E. Van Nieuwenhuyse 6, B-1160, Brussels, BELGIUM. Report No.: 3109/0060.

INHALATION

Omission of study (data waiver): An acute inhalation toxicity study does not need to be submitted as the most appropriate route of exposure is the dermal route.  Based on the current classification of the substance, further testing is likely to result in unnecessary animal suffering.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 November 2018 to 15 December 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-house bred animals
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 9 weeks
- Weight at study initiation: 162.1 g to 177.89 g
- Fasting period before study: Three animals per step were fasted overnight (16 to 18 hours) prior to dosing. Water was provided ad libitum during the fasting period. Feed was offered 3 to 4 hours after dosing.
- Housing: Three animals were housed in standard polypropylene cage with stainless steel mesh top grill. Clean sterilised paddy husk was provided as bedding material.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: Healthy young animas used for Step-I, Step-I confirmation, Step-II and Step-II confirmation were acclimatised for five, eight, eleven and thirteen days respectively to laboratory conditions prior to treatment and were observed for clinical signs once daily. Veterinary examination of all animals was performed on the day of receipt and on the 5th day of acclimatisation.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.3 - 22.9 °C
- Humidity (%): 47 % - 67 % relative humidity
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Justification for choice of vehicle: The test material formed uniform suspension in corn oil as evidenced by in-house solubility/suspensibility test. Hence, corn oil was selected for the test material formulation preparation. Corn oil is a universally accepted and routinely used vehicle in oral toxicity studies.
- Lot/batch no.: A1712001

MAXIMUM DOSE VOLUME APPLIED
- The dose volume administered to individual rats was adjusted according to its bodyweight recorded on the day of dosing. The dose volume was 10 mL/kg body weight.

DOSAGE PREPARATION
- The required quantity of test material was weighed, ground well using a pestle and mortar by adding a little volume of vehicle and transferred to a measuring cylinder. A small quantity of vehicle was added, rinsed and transferred into the measuring cylinder. Rinsing procedure was repeated until the complete transfer of contents to the measuring cylinder. Finally the volume was made up to the required quantity with vehicle to get the desired concentration.
- The freshly prepared test material formulation was used for administration. The homogeneity of the test material formulation was maintained by continuous stirring on a magnetic stirrer during dosing.

METHOD
- The freshly prepared test formulation was administered by oral gavage to each rat as a single dose using intubation cannula.
- The animals were dosed in a stepwise procedure with three female animals per step. A starting dose of 300 mg/kg body weight was selected from the fixed dose levels of 5, 50, 300 and 2000 mg/kg body weight as the LD50 of the test material was not available.
- The test material was administered by oral gavage as a single dose of 300 mg/kg body weight to three female rats in step-I. Clinical signs of toxicity and no mortality was observed at 300 mg/kg body weight in Step-I. Hence, as per the decision rules governing the sequential procedure presented in the OECD 423 guideline, Step-I confirmation was conducted using three more female rats after approximately 48 hours observation by administering a single dose of 300 mg/kg body weight of the test material. Clinical signs of toxicity and no mortality was observed at 300 mg/kg body weight in Step-I confirmation. Step-II was conducted using three more female rats after approximately 48 hours of observation by administering a single dose of 2000 mg/kg body weight. Clinical signs of toxicity and mortality were observed at 2000 mg/kg body weight in Step-II. Step-II confirmation was conducted using three more female rats after approximately 24 hours of observation by administering a single dose at 2000 mg/kg body weight. Clinical signs of toxicity and mortality were observed at 2000 mg/kg body weight in Step-II confirmation.
- Dose levels higher than 2000 mg/kg body weight were not tested.

Doses:

300 and 2000 mg/kg body weight

No. of animals per sex per dose:

Three females per step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All surviving animals were observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 hour (± 10 mins), 2 hours (± 10 mins), 3 hours (± 10 mins), and 4 hours (± 10 mins) post-dosing on day 1 and once daily thereafter for clinical signs of toxicity and twice daily for mortality during the 14 day observation period. Individual animal body weight was recorded on day 2 before test material administration and on day 8 and day 15 during the observation period. The body weight of dead animals was also recorded.
- Necropsy of survivors performed: Yes. At the end of the observation period, all surviving animals were humanely sacrificed under carbon dioxide asphyxiation, subjected to necropsy and a complete gross pathological examination and observations were recorded. In dead animals external gross changes were observed, hence tissues (stomach) were collected and preserved in 10 % neutral buffered formalin. Histopathological examination was not carried out on the collected tissues as per the sponsor’s request.
- Other examinations performed: Observations included changes in skin, fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system and somatomotor activity and behaviour pattern.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Mortality:

- In Step-I and Step-I confirmation, no mortality was observed.
- In Step-II on day 4 one animal was found dead; one animal revealed clinical signs and was found dead by afternoon observation. The surviving animal was found dead on day 6 observation.
- In Step-II confirmation all animals were found dead on Day 5 observation.

Clinical signs:

other: - In Step-I and Step-I confirmation, the animals were dosed at 300 mg/kg body weight. No clinical signs of toxicity and mortality were observed at 30 to 40 minutes; diarrhoea was observed at 1st, 2nd, 3rd and 4th hour observations. On day 2 clinical sig

Gross pathology:

- No gross pathological changes were observed in any of the surviving animals at 300 mg/kg body weight. However, in dead animals external gross change like wet perineum (6/6) and internal gross change like stomach haemorrhage (5/6) and autolysis (1/6) was observed.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of the study it was concluded that the LD50 cut off value for the test material was 500 mg/kg bodyweight.

Executive summary:

The test material was evaluated for acute oral toxicity in Sprague Dawley rats according to the standardised method OECD Guideline 423, under GLP conditions.

A starting dose of 300 mg/kg body weight was selected from the fixed dose levels of 5, 50, 300 and 2000 mg/kg body weight as the LD50 of the test material was not available.

A total of 12 females (3 females for each Step-I, Step-I confirmation, Step-II and Step-II confirmation) were used for the experiment. All animals of Step-I and Step-I confirmation were administered 300 mg/kg body weight of the test material formulation and Step-II and Step-II confirmation were administered with 2000 mg/kg body weight of the test material formulation through the oral route.

All surviving animals were observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 h (± 10 mins), 2 h (± 10 mins), 3 h (± 10 mins) and 4 hours (± 10 mins) post dosing on day 1 and once daily thereafter for clinical signs of toxicity and twice daily for mortality during the 14 day observation period. Body weight was recorded on day 1 before test material administration and on day 8 and day 15 during the observation period. At the end of the observation period, all surviving animals were sacrificed under carbon dioxide asphyxiation, subjected to necropsy and gross pathological examination.

In Step-I and Step-I confirmation the animals were dosed with 300 mg/kg body weight. Animals revealed clinical signs like diarrhoea and wet perineum. Clinical signs reversed back to normal by day 4 observation.

In Step-II and Step-II confirmation, the animals were dosed with 2000 mg/kg body weight. Animals revealed clinical signs like lethargy, diarrhoea, wet perineum and nasal discharge followed by death.

No changes were observed in body weight and percent change in body weight with respect to day 1 at 300 mg/kg body weight. All surviving animals revealed physiologically normal increase in the body weight.

No gross pathological changes were observed in any of the surviving animals at 300 mg/kg body weight. However, in dead animals external gross change like wet perineum (6/6) and internal gross change like stomach haemorrhage (5/6) and autolysis (1/6) was observed.

Under the conditions of the study it was concluded that the LD50 cut off value for the test material was 500 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 May 2010 to 02 June 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system 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:

other: There were no signs of systemic toxicity.

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:

other: Not classified according to EU criteria

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:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

ORAL

A number of existing studies are available which assess the acute oral toxicity of the test material with a widely varying range of results, from 164 mg/kg bw to > 10 000 mg/kg bw. The reliability of the studies is questionable, with the principle concern being the physical form of the substance that was tested and its purity and technical grade. In addition, lack of GLP, inadequate reporting of methods and lack of guidelines result in the existing data lacking reliability. This may go some way to explain the differences noted in the test results. In a study that was conducted according to a guideline there are concerns regarding the technical grade and physical state of the substance that was tested. The test material is a powder and a liquid formulation was used in the testing and insufficient detail was reported on the concentration of the test material within the formulation.

For other regulatory purposes, namely to address the concerns of other regulatory authorities regarding the classification of the substance and to identify an accurate LD50, a new study was conducted according to internationally recognised standardised guidelines, in compliance with GLP and with a known purity of the substance in the correct physical form. This new study (Bioneeds, 2019) has been selected as the key study with the other data included as supporting information. Accordingly, classification is based on the new study. The classification is substantiated by the only available supporting study with a reliable Klimisch rating of 2 (Bio/dynamics, 1980b).

 

Key Study: Bioneeds (2019)

The test material was evaluated for acute oral toxicity in Sprague Dawley rats according to the standardised method OECD Guideline 423. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997) as it is a new, well reported, GLP compliant study conducted according to an internationally recognised standardised method with no deviations.

A starting dose of 300 mg/kg body weight was selected from the fixed dose levels of 5, 50, 300 and 2 000 mg/kg body weight as the LD50 of the test material was not available.

A total of 12 females (3 females for each Step-I, Step-I confirmation, Step-II and Step-II confirmation) were used for the experiment. All animals of Step-I and Step-I confirmation were administered 300 mg/kg body weight of the test material formulation and Step-II and Step-II confirmation were administered with 2 000 mg/kg body weight of the test material formulation through the oral route.

All surviving animals were observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 h (± 10 mins), 2 h (± 10 mins), 3 h (± 10 mins) and 4 hours (± 10 mins) post dosing on day 1 and once daily thereafter for clinical signs of toxicity and twice daily for mortality during the 14 day observation period. Body weight was recorded on day 1 before test material administration and on day 8 and day 15 during the observation period. At the end of the observation period, all surviving animals were sacrificed under carbon dioxide asphyxiation, subjected to necropsy and gross pathological examination.

In Step-I and Step-I confirmation the animals were dosed with 300 mg/kg body weight. Animals revealed clinical signs like diarrhoea and wet perineum. Clinical signs reversed back to normal by day 4 observation.

In Step-II and Step-II confirmation, the animals were dosed with 2 000 mg/kg body weight. Animals revealed clinical signs like lethargy, diarrhoea, wet perineum and nasal discharge followed by death.

No changes were observed in body weight and percent change in body weight with respect to day 1 at 300 mg/kg body weight. All surviving animals revealed physiologically normal increase in the body weight.

No gross pathological changes were observed in any of the surviving animals at 300 mg/kg body weight. However, in dead animals external gross change like wet perineum (6/6) and internal gross change like stomach haemorrhage (5/6) and autolysis (1/6) was observed.

Under the conditions of the study it was concluded that the LD50 cut off value for the test material was 500 mg/kg bodyweight.

 

Supporting Studies:

Bio/dynamics Inc. (1980b)

The study was well documented, meets generally accepted scientific principles, and is acceptable for assessment. It is therefore awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study, the acute oral toxicity of the test material was assessed using five male and five female rats administered dose levels of 315, 397, 500, 630 or 794 mg/kg. Mortality, clinical signs and body weight were observed for 24 days.

Two of ten animals, one male and one female, died at 500 mg/kg dose.

Soft stool, faecal staining and an ungroomed or unthrifty appearance were seen in some rats at all dosages. Other signs were noted. Most animals at all doses were free of significant in-life observations within 14 days after dosing.

Two animals, one male and one female, dying prior to the termination of the study exhibited weight loss. The majority of animals on this study exhibited body weight gains over the 24 day post-dose observation period. One female exhibited a slight weight loss at 24 days.

Under the conditions of the study, the acute oral LD50 of the test material can be considered > 794 mg/kg.

 

Schering AG, Experimentelle Toxikologie (1971)

The study was awarded a reliability score of 4 in accordance with the criteria set forth by Klimisch et al. (1997). Most of this report is written in German, only a short summary of the data available as a translation. Furthermore, there is insufficient information available on the test material.

Mortality (deaths/total animals exposed):

250 mg/kg: 8/10 (2 males)

350 mg/kg: 5/10 (2 males, 3 females)

500 mg/kg: 5/10 (4 males, 1 female)

700 mg/kg: 5/10 (3 males, 2 females)

1 000 mg/kg: 8/10 (3 males, 5 females)

1 400 mg/kg: 9/10 (5 males, 4 females)

The LD50 was determined to be 497 mg/kg.

 

von Klimmer (1969)

The study was awarded a reliability score of 4 in accordance with the criteria set forth by Klimisch et al. (1997) due to insufficient documentation on the study methods and insufficient information available on the test material.

The LD50 of the test material dosed orally in male rats was reported as 520 mg/kg (oil suspension) and 800 mg/kg (Tylosesuspension).

 

Bio/dynamics Inc. (1980a)

The study was awarded a reliability score of 4 in accordance with the criteria set forth by Klimisch et al. (1997) due to insufficient documentation and insufficient information on the test material.

The acute oral toxicity of the test material was assessed using five male and five female rats administered dose levels of 315, 397, 500, 630 or 794 mg/kg. Mortality, clinical signs and body weight were observed for 24 days. 

Of the ten animals one male died at the 630 mg/kg dose level.

Soft stool, faecal staining, motor activity decrease and ungroomed or unthrifty appearance were seen in some rats at all dosages within four days at dosages of 397 mg/kg and below and within 14 days at dosages of 500 mg/kg and above.

During the post-dose observation period one male from the 630 mg/kg dose died exhibiting weight loss before death. All other animals survived and exhibited body weight gains over the 24 day observation period.

Under the conditions of the study, the acute oral LD50 of the test material can be considered > 794 mg/kg.

 

Ciba-Geigy Ltd. (1972)

The study was awarded a reliability score of 3 in accordance with the criteria set forth by Klimisch et al. (1997). Insufficient documentation of test substance purity, test method, and observation details were provided.

The acute oral LD50 of TK-11285 in rats of both sexes observed over a period of 7 days is greater than 10 000 mg/kg. The compound has therefore a slight acute toxicity to the rate by this route of administration.

 

Thevenaz (1983)

The study was awarded a reliability score of 4 in accordance with the criteria set forth by Klimisch et al. (1997) since there is insufficient information available on the test material.

Under the conditions of this study, upon an acute oral administration and a 14-day post-treatment observation period, the following LD50s were calculated:

LD50 (male): 176 (108 -303) mg/kg bw

LD50 (female): 164 (65 -322) mg/kg bw

LD50 (male/female): 172 (121 -240) mg/kg bw

Clinical observations and effects on bodyweight were noted at a number of doses along with potential behavioural changes. According to the company standard, the test material shows medium acute toxicity.

 

M&T Chemicals, Inc. (1977)

The study was awarded a reliability score of 4 in accordance with the criteria set forth by Klimisch et al. (1997)since there is insufficient information available on the test material.

An acute oral toxicity study was performed with Wistar albino rats using test material "thermolite 15, JCRDY-611K, 4201. They observed mortality and overt signs of effects for 14 days. A gross necropsy was performed on all animals dying spontaneously. The oral LD50 was 260 mg/kg with 95 % confidence limits of 209 and 311 mg/kg. Common signs of effects during this study included: Ataxia, red nasal discharge, urinary staining of the abdomen, soft stool, piloerection, lethargy and faecal staining.

 

 

DERMAL

In the key dermal study (Sanders, 2010) the acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2 000 mg/kg bodyweight, according to OECD methods. A reliability rating of 1 was assigned (according to the criteria of Klimisch, 1997). The study was performed in compliance with GLP.

 

 

INHALATION

Omission of study (data waiver): An acute inhalation toxicity study does not need to be submitted as the most appropriate route of exposure is the dermal route.  Based on the current classification of the substance, further testing is likely to result in unnecessary animal suffering.

Justification for classification or non-classification

According to Regulation No. (EC) No 1272/2008 this substance is assigned to Acute Toxicity category 4 (Hazard statement: H302: Harmful if swallowed).

No classification for acute dermal toxicity is required.