Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Cross-referenceopen allclose all
Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 Sep 2014 to 21 July 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
ANIMALS AND ANIMAL HUSBANDRY- Five male and five female 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 animals were housed individually during the 24 hour exposure period and in groups of five, 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.- 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.
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.- Using available information on the toxicity of the test item, a single group of animals was treated.- The calculated volume of test item was 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 gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.- The animals were caged individually for the 24-hour exposure period.- After the 24 hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with suitable vehicle to remove any residual test item.- Animals were returned to group housing for the remainder of the study period.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
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 (1.079) and used to calculate the appropriate dose volume (1.86 mL/kg) 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.
Key result
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.
Body weight:
- Individual body weights and body weight changes are shown in Table 4 (attached).- Animals showed expected weight gain with the exception of one female, which showed body weight loss during the first week but expected gain in body weight 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.

- Individual clinical observations and mortality data are given in Table 1 (attached).

Interpretation of results:
GHS criteria not met
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 bw.
Executive summary:

GUIDELINE

OECD Guidelines for the Testing of Chemicals No 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No 440/2008.

METHODS

A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg bw. 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: There were no signs of dermal irritation.

Body weight: Animals showed expected gains in body weight except for one female, which showed body weight loss during the first week but expected gain in body weight 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 bw.

Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 December 1987 to 11 january 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
other: 16 CFR Part 1500
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Charles River Breeding laboratories, Inc, Wilmington, MA- Age at study initiation: Young adult-Weight at study initiation: 224 to 316g- Fasting period before study: Overnight before day of dosing- Housing: Individually in wire mesh bottom cages- Diet (e.g. ad libitum): NIH Open Formula 07 (Zeigler Brothers) ad libitum- Water (e.g. ad libitum): tap water ad libitum- Acclimation period: Minimum of 5 daysENVIRONMENTAL CONDITIONSConformed to standards established in "Guide for the care and use of Laboratory animals" DHEW Publication No (NIH) 85-23.IN-LIFE DATES: From: 28 December 1987 To: 11 January 1988
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE- Concentration in vehicle: None, dosed as suppliedMAXIMUM DOSE VOLUME APPLIED: Not reported
Doses:
5000 mg/kg
No. of animals per sex per dose:
5/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 Days- Frequency of observations and weighing: Three times on day of dosing, daily thereafter.- Necropsy of survivors performed: yes- Other examinations performed: clinical signs, body weight,
Statistics:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No premature deaths were recorded. All animals survived to study termination (Day 15).
Clinical signs:
Decreased acitivity, diarrhea and apparent urinary incontinence were noted following dose administration. Three female rats exhibited hair loss on the hind legs. This finding started on days 5, 9 and 12, respectively, and continued to the end of the study for all three animals.
Body weight:
The test article administration did not cause an adverse effect upon mean body weight in either sex.
Gross pathology:
No gross lesions were noted in the five male and five female rats examined grossly at study termination.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material gave an LD50 value greater than 5000 mg/kg in the rat.
Executive summary:

Test Guidance

US EPA 16 CFR Part 1600.

Method

The test substance was administered by gavage to each of five male and five female Sprague-Dawley rats at a dose level of 5000 mg/kg body weight. The animals were observed for pharmacotoxic signs and mortality for 15 days.

Results

All animals survived the 15 day post-adminstration period.

Conclusion

The test material gave an LD50 value greater than 5000 mg/kg in the rat.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion