2'-methylacetoacetanilide

Endpoint summary

Description of key information

In the OECD SIDS key study mortality was oberserved at 1280 mg/kg dose level for males and at 1600 mg/kg for females, 
further deaths at 2000 mg/kg dose level for males and females. 
Therefore, the LD50 value by oral for rat is 1854 mg/kg for male and 1945 mg/kg for female. 
In the supporting study no animals died during the observation period.
Therefore, the LD50 of test item AAOT is > 5000 mg/kg.

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:

supporting study

Study period:

1979-07

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable for reliability but not in detail documented. Study report meets basic scientific principles. Study was conducted prior to GLP and OECD guideline implementation.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Study was conducted and reported in accordance with the agreed protocol, and with the Hazleton Manual of Standard Operating Procedures.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals: 13 male and 13 female Wistar rats
Source: Bantin and Grimston, Aldbrough, Nr. Hull, HUII 4QE
Environment: They were conditioned to the laboratory environment for not less than 3 days
Body weights: 125 — 225 g
Diet: With the exception of the overnight fast (for 18—20 hours before treatment) the animals were allowed free access to mains
water and food (Rat and Mouse No. 1 Expanded Diet, BP Nutrition (U.K.) Ltd., Witham, Essex). The food was reintroduced immediately after dosing.
Environment: All animals were housed in a single air—conditioned room maintained at a mean
Temperature: Between 19 — 25°C,
Relative humidity: Between 40 — 60%
Light: Exposed to natural lighting conditions.
They were caged in groups of 2 or 5 by sex as appropriate in solid floor polypropylene boxes furnished with softwood sawdust. Sawdust was replaced
twice per week.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

A single oral dose of test article, based on the fasted body weight of the animals at the time of treatment, was
administered by gavage using a metal stomach tube. The animals were then returned to
their cages for observation.

Doses:

250 mg/kg
500 mg/kg
1000 mg/kg
2000 mg/kg
5000 mg/kg

No. of animals per sex per dose:

Group 1: 2 males and 2 females
Group 2: 2 males and 2 females
Group 3: 2 males and 2 females
Group 4: 2 males and 2 females
Group 5: 5 males and 5 females

Control animals:

no

Details on study design:

Dose range finding study — phase 1:
---------------------------------
Four groups each of 4 fasted rats (2 males, 2 females) and one group of 10 fasted rats (5 males, 5 females) were dosed.
Animals were observed for mortality over the following 48 hours.
Treatment volume 10 ml/kg.

Dose range finding study — phase 2:
---------------------------------
Mortality at a level of 50% or greater in any group did not occur during phase 1 and the surviving animals in groups 1—4 were killed.
The group 5 animals were retained for observation for a further 12 days.

Observations on the group 5 animals:
---------------------------------
Animals were observed for overt signs of toxicity and behavioural change at 0.25‚ 1, 2 and 4 hours after treatment and subsequently once daily for 14 days
and the observations were recorded. Individual body weights were recorded on the day before treatment, on the day of treatment and at 7 and 14 days after
treatment. All animals surviving at the end of the observation period were killed by inhalation of excessive levels of carbon dioxide.

Statistics:

Not available.

Preliminary study:

Not applicable.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died during the observation period.

Clinical signs:

other: All male animals and 1 female animal showed lethargy or prostration throughout the day of dosing. Lethargy was also noted in all male animals 24 hours after treatment. Both male and female animals appeared anaemic with dark red eyes 24 and 48 hours after

Gross pathology:

No necropsies were performed.

Other findings:

No other findings available.

Mortality and time of death during the observation period:

Dose level mg/kg	No. of animals / sex	Number of deaths during									Cumulative mortality
		Day of dosing	Observation day
			1	2	3	4	5	6	7	8-14
5000	5 males	0	0	0	0	0	0	0	0	0	0/5
5000	5 females	0	0	0	0	0	0	0	0	0	0/5

Group mean body weights (g):

Dose level mg/kg	No. of animals / sex	Group mean body weights on
		Day before treatment	Day 7	Day 14
5000	5 males	170	212	251(5 animals)
5000	5 females	149	163	171(5 animals)

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute oral median lethal dose (LD50) of test item AAOT is > 5000 mg/kg.

Executive summary:

The study was conducted prior to GLP and OECD guideline implementation.

Acceptable for reliability but not in detail documented. Nevertheless, the study report meets basic scientific principles.

This study was undertaken to determine the oral median lethal dose (LD50) of test article P0012 in Wistar rats. The study was performed during July 1979.

No animals died during the observation period. All clinical signs disappeared from day 3 of observation until termination on day 14.

Normal increases in mean body weight were shown by both male and female animals at the day 7 and day 14 weighings.

Therefore, the LD50 of test item AAOT is > 5000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 854 mg/kg bw

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:

adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Additional information

An oral rat study (MHW Japan, 1999a, OECD SIDS Dossier) is identified as the best quality and the key study, because it was well conducted according to OECD TG401, following GLP and described in detail. In the Single Dose Oral Toxicity test in rats; AAOT was administered at the doses of 0, 819, 1024, 1280, 1600, 2000, 2500 mg/kg to both sexes.

The first mortality was oberserved at 1280 mg/kg dose level for males and at 1600 mg/kg for females, further deaths at 2000 mg/kg dose level for males and females. Dead animals showed serious those clinical signs and weak respiration before die.

Therefore, the LD50 value by oral for rat is 1854 mg/kg for male and 1945 mg/kg for female.

The supporting study was conducted prior to GLP and OECD guideline implementation. Acceptable for reliability but not in detail documented. Nevertheless, the study report meets basic scientific principles. This study was undertaken to determine the oral median lethal dose (LD50) of test article P0012 in Wistar rats. The study was performed during July 1979.

No animals died during the observation period. All clinical signs disappeared from day 3 of observation until termination on day 14.

Normal increases in mean body weight were shown by both male and female animals at the day 7 and day 14 weighings.

Therefore, the LD50 of test item AAOT is > 5000 mg/kg.

Justification for selection of acute toxicity – oral endpoint
key study, also see IUCLID section 7.5.1 Repeated dose toxicity: oral
Toxicological effects and the target organs are hemolytic anemia and the related changes on the blood, spleen, liver and kidney,
including male kidney (increasing of eosinophilic bodies) and female liver (increasing of the weight).

Justification for selection of acute toxicity – inhalation endpoint
Toxicological effects and the target organs are hemolytic anemia and the related changes on the blood, spleen, liver and kidney,
including male kidney (increasing of eosinophilic bodies) and female liver (increasing of the weight).

Justification for selection of acute toxicity – dermal endpoint
Toxicological effects and the target organs are hemolytic anemia and the related changes on the blood, spleen, liver and kidney,
including male kidney (increasing of eosinophilic bodies) and female liver (increasing of the weight).

Justification for classification or non-classification

The key study which was performed according to the OECD Guideline 401 and principles of GLP, the LD50 value by oral for rat is 1854 mg/kg for male and 1945 mg/kg for female.

Therefore, the substance will be classified as harmful (H 302) according to GHS.

Considering the results of Repeat Dose Toxicity study (see section 7.5.1), those toxic effects are assumed to be caused by hemolytic anemia.