N-(5-chloro-2-methoxyphenyl)-2-[(2-methoxy-4-nitrophenyl)azo]-3-oxobutyramide

Endpoint summary

Description of key information

Acute oral toxicity: Key study. Test method according to OECD 401, GLP study. Single application of the limit dose of 2000 mg test substance per kg bw did not cause lethality in male and female Sprague-Dawley rats during the 14 day observation period, resulting in a LD50 > 2000 mg/kg bw.

Acute inhalation toxicity: Data waving: According to REACH Annex VIII, No. 8.5, Column 2 in addition to the oral route, information shall be provided for at least one other route. Oral and dermal acute toxicity data are available.

Acute dermal toxicity: Key study. Test method according to OECD 402, GLP study. 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.

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:

From 13 MAY 1998 to 27 MAY 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 401) GLP compliant

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

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 or test system and environmental conditions:

TEST ANIMALS
- Strain: HSD: Sprague Dawley SD
- Source: Harlan Winkelmann, Borchen, Germany, SPF breeding colony
- Age at study initiation: 6 - 10 weeks
- Weight at study initiation: males mean +/- SD: 204 +/- 11.6 g; females mean +/- SD: 180 +/- 4.3 g
- Fasting period before study: yes (no further information)
- Housing: in Makrolon cages (Type 4) in groups of 5
- Diet: ssniff R/M-H (V1534), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- fully air-conditioned rooms
- Temperature (°C): 22+/-3
- Humidity (%): 50+/-20
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Doses:

limit dose: 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Frequency of observations: twice every day/weekends and holidays only once
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no animals died within the observation period

Mortality:

- no deaths occurred

Clinical signs:

other: other: - no signs of toxicity observed - faeces was yellow- coloured in all animals on day 2 and 3 of the study

Gross pathology:

- animals killed at the end of the observation period showed no macroscopically visible changes

Interpretation of results:

other: Non classified

Conclusions:

Single application of the limit dose of 2000 mg test substance per kg bw did not cause lethality in male and female Sprague-Dawley rats during the 14 day observation period, resulting in a LD50 > 2000 mg/kg bw.

Executive summary:

Male and female Sprague-Dawley rats (5 per sex) were subjected to test acute oral toxicity according to OECD TG 401. The test substance was administered by gavage at the limit dose of 2000 mg/kg bw.. No animal died during the 14 day observation period, resulting in a LD50 > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Key study with klimisch score = 1

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

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:

From 07 DEC 2011 to 21 DEC 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 402) and according to GLP.

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

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:

Five male and five female Wistar (RccHan:WIST) strain rats.
On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals weighed at least 200g, and were eight to twelve weeks of age. The weight variation did not exceed ±20% of the mean weight for each sex.

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. Free access to mains drinking water and food 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.

The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve 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.

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Details on dermal exposure:

The appropriate amount of test item, mixed with arachis oil BP, was applied as evenly as possible to an area of shaved skin (approximately 10% of the total body surface area).

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 Male
5 Female

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Frequency of observations: first day: 4 times, thereafter once daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, dermal reactions

Statistics:

No statistical analysis was performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no animal died within the observation period

Mortality:

There were no deaths.

Clinical signs:

other: other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Dermal Reactions

Yellow coloured staining was noted at the test sites of all animals during the study. The staining prevented accurate evaluation of erythema in all animals one day after dosing.
Very slight erythema was noted at the test site of one female five to eight days after dosing. Crust formation and small superficial scattered scabs were also noted at this site. There were no signs of dermal irritation noted in the remaining animals.

Interpretation of results:

other: Not classified

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 bodyweight.

Executive summary:

Introduction.  The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat. The method was designed to be compatible with the following:

OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)

Method B3 Acute Toxicity (Dermal) of CommissionRegulation (EC) No. 440/2008

Method.

A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the test item 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. 

There were no deaths.

Clinical Observations. 

There were no signs of systemic toxicity.

Dermal Irritation. 

Very slight erythema was noted at the test site of one female. Crust formation and small superficial scattered scabs were also noted at this site. No other signs of dermal irritation were noted. 

Bodyweight. 

Animals showed expected gains in bodyweight over the study period except for one female which showed expected gain in bodyweight during the first week but slight bodyweight loss 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 bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Justification for classification or non-classification

Based on the available data, the substance is not classified for acute toxicity according to CLP Regulation (EC) no. 1272/2008.