C8-18 alkylampho(di)propionates

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 16, 2012 - November 23, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study has been performed in accordance with OECD 402 (1987), EU Method B.3 (2008), EPA OPPTS 870.1200 (1998) and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1987)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

(1998)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

other: aqueous solution

Details on test material:

- Physical state: Aqueous solution
- Appearance: Colourless to pale yellow liquid
- Composition of test material, percentage of components: see section confidential details on test material

Test animals

Species:

rat

Strain:

other: Wistar strain, Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing (during the acclimatization period): group housed in Makrolon cages
- Housing (after application): Individually housed in labeled Makrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24
- Humidity (%): 40 to 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

- Clipping: One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped
- Application: The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
- Frequency: Single dosage, on Day 1.
- Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.

Duration of exposure:

24 hours

Doses:

5189.5 mg/kg bw (expressed as registered substance) which corresponds to 2000 mg/kg bw expressed as solid content

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Dose volume: 4.85 mL/kg bw (Density: approx. 1.07 g/mL)
- Dosage preparation: The test substance was dosed undiluted. Correction was made for the solid content of the test substance (a correction factor of 2.59 was used)
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 189.5 mg/kg bw

Based on:

test mat.

Remarks:

(aqueous solution)

Remarks on result:

other: Aqueous solution with a solid content of 38.56%

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

other: expressed as solid content

Mortality:

No mortality occurred

Clinical signs:

other: - Flat posture was shown by one male on Day 1. Chromodacryorrhoea was shown by one male and one female on Day 1 - Focal erythema (grade 1) was seen on the treated skin-area of all males on Days 2 and 3

Gross pathology:

- Pelvic dilation of the kidneys, reddish foci on the thymus or discolouration of the thymus were shown by three males
- Macroscopic examination of the other animals did not reveal any abnormalities

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an acute dermal toxicity study with rats, performed according to OECD/EC test guidelines, a LD50 of > 5189.5 mg/kg bw was determined.

Executive summary:

The acute dermal toxicity of the substance was determined in the rat, in accordance with OECD 402 (1987), EU Method B.3 (2008), EPA OPPTS 870.1200 (1998) and according to GLP principles. The substance was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight (expressed as solid content) for 24 hours (a correction factor of 2.59 was used). The dose corresponded to 5189.5 mg/kg bw for the registered substance.

No mortality occurred. Flat posture was shown by one male on Day 1. Chromodacryorrhoea was shown by one male and one female on Day 1. Focal erythema (grade 1) was seen on the treated skin-area of all males on Days 2 and 3. The changes noted in body weight gain in males and females were considered not indicative of toxicity. Pelvic dilation of the kidneys, reddish foci on the thymus or discolouration of the thymus were observed by three males. Macroscopic examination of the other animals did not reveal any abnormalities. The dermal LD50 value of the substance in Wistar rats was established to exceed 5189.5 mg/kg bw, which corresponds to > 2000 mg/kg body weight expressed as solid content.