bis(branched-alkyl) 2-{[(1-phenylethyl)amino]methyl}alkanedioate

Acute Toxicity: dermal

Some information in this page has been claimed confidential.

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 January 2015 to 10 April 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Details on test material:

- Physical state: Pale amber liquid
- Analytical purity: 100 %
- Expiration date of the lot/batch: 08 January 2017
- Storage condition of test material: approximately 4 °C in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMALS AND ANIMAL HUSBANDRY
- Five male and five femal Wistar (RccHan: WIST) strain rats were supplied by Harlan Laboratories Ltd, Oxon, UK.
- The animals were randomly allocated to cages on receipt.
- Female animals were nulliparous and non-pregnant.
- After an acclimatisation period of at least 5 days, animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and recording of the number on a cage card.
- Animals weighed at least 200 g and were 8 to 12 weeks of age at the start of the study.
- The weight variation did not exceed ± 20 % of the mean weight for each sex.
- Animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes.
- The initial two animals were housed individually throughout the study.
- The further group of eight animals (four male and four female) were housed individually during the 24 hour exposure period and in groups of four, by sex, for the remainder of the study.
- Free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories Ltd, Oxon, UK) was allowed throughout the study.
- The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively.
- The rate of air exchange was at least fifteen changes per hour.
- Lighting was controlled by a time switch to give 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.
- The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

PROCEDURE
- On the day before treatment, the back and flanks of each animal were clipped free of hair.
- In the absence of data suggesting the test item was toxic, one male and one female rat were initially treated with the test item at a dose level of 2000 mg/kg (specific gravity 0.967; dose volume 2.07 mL/kg).
- The calculated volume of test item, as received, waas applied as evenly as possible to an area of shorn skin (approximately 10 % of the total body surface area) using a graduated syringe.
- A piece of surgical guaze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.
- The animals were caged individually throughout the study.
- Shortly after dosing the dressings were examined to ensure they were securely in place.
- 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 item.
- As no mortalities were noted, a further group of animals (four males and four females) was similarly treated with test item at a dose level of 2000 mg/kg bw . The animals were caged individually for the 24 hour exposure period.
- After the 24 hour contact period, the bandages were carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item.
- The four males and four female animals were returned to group housing for the remainder of the test period.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

TEST ITEM FORMULATION AND EXPERIMENTAL PREPARATION
- The test item was used as supplied.
- Specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.
- Absorption of the test item was not determined.

Statistics:

- Data evaluations included the relationsip, if any, between exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, body weight changes, mortality and other toxicological effects.
- Using the mortality data obtained, and estimate of the acture dermal median lethal dose (LD50) of the test item was made.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- No animal deaths took place.

Clinical signs:

- No signs of systemic toxicity were noted during the observation period (see Table 1, attached).

Body weight:

- Individual body weights and body weight changes are shown in Table 4 (attached).
- Animals showed expected gains in body weight with the exception of two animals which showed body weight loss or no gain in body weight during the first week. The expected gain in body weight took place during the second week.

Gross pathology:

- Individual necropsy findings are given in Table 5 (attached).
- No abnormalities were noted at necropsy.

Other findings:

DERMAL REACTIONS
- Individual dermal reactions are shown in Tables 2 and 3 (attached).
- No signs of dermal irritation were observed.

Applicant's summary and conclusion

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 item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Executive summary:

GUIDELINE

Acute dermal toxicity was investigated in the Wistar rat using a method designed to be compatible with OECD Guidelines for the Testing of Chemicals No 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method B.3 Acute Toxicity (Dermal) of Commission Regulation (EC) No 440/2008.

METHOD

Initially, two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bw. Based on the results of the initial test, a further group of eight animals (four males and four females) were treated similarly. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

RESULTS

Mortality: No animal deaths took place during the study.

Clinical observations: No signs of systemic toxicity were observed.

Dermal irritation: No signs of dermal irritation were observed.

Body weight: Animals showed expected gains in body weight with the exception of two animals which showed body weight loss or no gain in body weight during the first week. The expected gain in body weight took place during the second week.

Necropsy: No abnormalities were noted at necropsy.

CONCLUSION

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