2,6-difluorobenzamide

Endpoint summary

Description of key information

Oral route: The LD50 was 1075 mg/kg bw for female rats and 2576 mg/kg bw for male rats.
Dermal route: The LD50 was >2000 mg/kg bw for male and female rats.

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:

Sep - Oct 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Non-GLP, near guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K., Ltd.
- Age at study initiation: 9 to 11 weeks
- Fasting period before study: animals were fasted overnight (18 hours)
- Weight at study initiation: 190 g (males) and 138 g (females)
- Housing: single sex groups of 2-3 in cages with stainless-steel wire-mesh floors and tops; each cage measured 38 x 25 x 18 cm
- Diet: PRD (Labsure animal Foods, Dorset, UK), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50% in DMSO (m/v)

Doses:

780-3200 mg/kg bw

No. of animals per sex per dose:

780 mg/kg bw: 4
1250 mg/kg bw: 8
1500 mg/kg bw: 4
2000 mg/kg bw: 8
2500 mg/kg bw: 4
3200 mg/kg bw: 4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days;
- Frequency of observations and weighing: Observations were recorded three times a day for the first three days and daily thereafter. The initial (i.e. day 1), day 7 and day 14 body weights were recorded;
- Necropsy of survivors performed: no;
- Other examinations performed: clinical signs and body weight.

Statistics:

prohibit analyis

Sex:

male

Dose descriptor:

LD50

Effect level:

2 576 mg/kg bw

Based on:

test mat.

Remarks on result:

other: given the disparity in response between males and females, a combined LD50 values is not quoted

Sex:

female

Dose descriptor:

LD50

Effect level:

1 075 mg/kg bw

Based on:

test mat.

Remarks on result:

other: given the disparity in response between males and females, a combined LD50 values is not quoted

Mortality:

780 mg/kg bw: males: 0/4; females: 0/4
1250 mg/kg bw: males: 0/8; females: 6/8
1500 mg/kg bw: males: 0/4; females: 4/4
2000 mg/kg bw: males: 1/8; females: 8/8
2500 mg/kg bw: males: 1/4; females: 4/4
3200 mg/kg bw: males: 4/4; females: 4/4

Clinical signs:

other: The incidence and duration of clinical signs were dose-related. The commonest clinical signs seen indicated a neurological action since they included gait and posture abnormalities and prostration, the sequela to the latter being coma in some cases.

Gross pathology:

Not investigated.

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test item in female rats was calculated to be 1075 mg/kg bw and in male rats 2576 mg/kg bw.

Executive summary:

The acute oral toxicity of the test substance was investigated in Fischer 344 rats. The test substance was administered orally by gavage at 780, 1250, 1500, 2000, 2500 and 3200 mg/kg bw. Animals were subjected to observations and determination of the body weight. Mortality occurred at concentrations from 1250 up to 3200 mg/kg bw in females and from 2000 up to 3200 mg/kg bw in males. The incidence and duration of clinical signs were dose-related. The commonest clinical signs seen indicated a neurological action since they included gait and posture abnormalities and prostration, the sequela to the latter being coma in some cases. All surviving animals had gained weight relative to their day 1 bodyweights by the end of the 14 day observation period.

The acute oral median lethal dose (LD50) of the test item in female rats was calculated to be 1075 mg/kg bw and in male rats 2576 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 075 mg/kg bw

Quality of whole database:

The whole database is of good quality.

Acute toxicity: via inhalation route

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Non-GLP, near guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K., Ltd.
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: 220 g (males) and 151 g (females)
- Housing: single sex groups of 2-3 in cages with stainless-steel wire-mesh floors and tops; each cage measured 38 x 25 x 18 cm
- Diet: PRD (Labsure animal Foods, Dorset, UK), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

occlusive

Vehicle:

other: moistened powder

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal site
- % coverage: 60% of dorsal site
- Type of wrap if used: aluminium foil lined with gauze , fixed by a double overwrap of waterproof adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing: with warm dilute detergent solution and then dried
- Time after start of exposure: 24 h

Duration of exposure:

24 hours

Doses:

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 observations and weighing: Observations were recorded three times a day for the first three days and daily thereafter. The initial (i.e. day 1), day 7 and day 14 body weights were recorded;
- Necropsy of survivors performed: no;
- Other examinations performed: clinical signs and body weight.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: no effects

Gross pathology:

not investigated

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the median lethal dose of the test item after dermal application was found to be greater than 2000 mg/ka bw.

Executive summary:

The acute dermal toxicity of the test item was evaluated on the basis of a study similar to the OECD guideline 402.

There were no clinical signs and all rats had gained weight relative to their day 1 bodyweights ba the end of the 14 day observation perios. None of the rats died from which it was concluded that the acute dermal median lethal dose (LD50) of the test item, applied as a moistened powder, in rats was greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The whole database is of good quality.

Additional information

Oral toxicity

In an acute oral toxicity study comparable to OECD guideline 401, rats (Fisher 344, 4-8/sex/dose) were exposed to 780-3200 mg/kg bw 2,6-difluorobenzamide in DMSO (50%) by gavage and were observed for 14 days (Sittingbourne Research Centre, 1987). The incidence and duration of clinical sings were dose-related. The commonest clinical signs observed indicated a neurological action since they included gait and posture abnormalities and prostration, the sequela to the latter being coma in some cases. All surviving animals had gained weight relative to their day 1 bodyweights by the end of the 14 day observation period. Mortality figures were as follows: no mortality was observed at 780 mg/kg bw in both sexes, 0/8 males and 6/8 females died at 1250 mg/kg bw, 0/4 males and 4/4 females died at 1500 mg/kg bw, 1/8 males and 8/8 females died at 2000 mg/kg bw, 1/4 males and 4/4 females died at 2500 mg/kg bw and 4/4 males and 4/4 females died at 3200 mg/kg bw. No gross pathology was performed. The LD50 was 2576 mg/kg bw in male rats and 1075 mg/kg bw in female rats.

 

Dermal toxicity

In an acute dermal toxicity test, comparable to OECD guideline 402, rats (Fisher 344, 5/sex) were treated with 2000 mg/kg bw 2,6-difluorobenzamide applied as a moistened powder for 24 hours and subsequently observed for a 14-day period (Sittingbourne Research Centre, 1987). No mortality, clinical signs or effects on bodyweight were observed. No gross pathology was performed. The LD50 was determined to be >2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Most reliable study.

Justification for selection of acute toxicity – dermal endpoint
Most reliable study.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is considered to be classified for acute toxicity under Directive 67/548/EEC, as amended for the 31st time in Directive2009/2/EC with Xn, R22.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is considered to be classified for acute toxicity under Regulation (EC) No 1272/2008, as amended for the fifth time in Directive EC 944/2013, the classification is H302, Cat. 4.