Butanedioic acid, sulfo-, monoesters with lanolin alcs., disodium salts

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

Between 23 March 2010 and 6 April 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Data have been obtained from a study on a substance with structural similarity. GLP Compliance statement (OK GLP standards); GLP standards published as OECD (ENV/MC/CHEM(98)17); Requirements of Directives 2004/9/EC and 2004/10/EC.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p 31: evaluation and skin reactions.

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Lanoline Alcohols

IUPAC Name:

Lanoline Alcohols

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan laboratories UK Limited
- Females were nulliparous and non-pregnant.
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: at least 200 g. The variation did not exceed ± 20% of the mean weight for each sex.
- Acclimation period: at least five days
- Marking: number unique within the study by indelible ink-marking on the tail and a number written on a cage card.
- Housing: On receipt the animals were randomly allocated to cages. Rats housed in suspended solid-floor polypropylene cages furnished with woodflakes. Animals were housed individually during the 24 hour exposure period and in group of five, by sex.
- Diet: ad libitum, Teklad Global Rodent diet supplied by Harlan Teklad, UK.
- Water: ad libitum
The diet, drinking water and bedding were routinely analysed and considered not to contain any contaminants.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): limits of 19 - 25 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes
- Photoperiod (hrs dark / hrs light): lighting controlled by a time switch, to have twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Details on dermal exposure:

TEST SITE
- pre-treatment: on day before treatment the back and lanks of each animal were clipped free of hair.
- Area of exposure: 10% of the total body surface area.
- Type of wrap if used: a piece of surgical gauze with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Wipping: after the 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: animals were caged individually for the 24 hours exposure period.
Shortly after dosing the dressing were examined to ensure that they were securely in place.

TEST MATERIAL
- Amount applied: 2000 mg/kg with arachis oil BP.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males
5 females

Details on study design:

- Duration of observation period following administration: 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Necropsy of survivors performed: yes, rats were killed by cervical dislocation. The gross necropsy 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.
- Other examinations performed: once daily for fourteen days the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity tests" Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and
Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p 31: evaluation of skin reactions (table 1).
- Individual bodyweights were recorded prior to application of the test material on Day 0 and on Day 7 and 14.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths

Clinical signs:

other: No signs of systemic toxicity No Individual dermal reactions for males No Individual dermal reactions for females No signs of dermal irritation

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

other: not classified as harmful/toxic according to the CLP Regulation (EC) No.1272/2008

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.

Mortality, no signs of systemic toxicity and no signs of dermal irritation were observed. No abnormalities were noted at necropsy.

Animals showed expected gains in bodyweight over the study period except for one female which showed no gain in bodyweight during the first week with expected gain in bodyweight during the second week.

It could be concluded that the acute dermal median lethal dose (LD5o) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.