Registration Dossier

Administrative data

Endpoint:
methaemoglobinaemia
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented study report which meets basic scientific principles. Study was conducted priore to GLP implementation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: company guideline
Deviations:
no
Principles of method if other than guideline:
Test animal: cat
Route of exposure: gavage
Examinations/observations: Clinical signs, lethality, Methemoglobin concentration
GLP compliance:
no
Remarks:
prior to GLP implementation
Type of method:
in vivo
Endpoint addressed:
acute toxicity: oral

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Acetessig-m-xylidid

Test animals

Species:
cat
Strain:
not specified
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
VEHICLE

- Concentration in vehicle: 2.0 or 0.5 % (aqueous suspension)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
observation period: 14 d
Frequency of treatment:
once
Post exposure period:
14 d
Doses / concentrations
Remarks:
Doses / Concentrations:
200 or 50 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
200 mg/kg bw: 2 male, 4 female
50 mg/kg bw: 1 male, 1 female
Control animals:
other: blood sampling before treatment

Examinations

Examinations:
Clinical signs, lethality, Methemoglobin concentration
Positive control:
no

Results and discussion

Details on results:
200 mg/kg bw:
Lethality: 3/6
MetHb concentration: Slightly increased except one surviving animal which showed a distinct increase
Clinical signs: Apathy, salivation, ataxic gate, crying, prone position, lateral position, decreased feed consumption

50 mg/kg bw:
Lethality: 0/2
MetHb concentration: Very slightly increased
Clinical signs: no abnormal findings

Any other information on results incl. tables

Dose

Animal no / sex

Fate

Methemoglobin concentration (%)

Before application

4 h post apllication

3 d post application, cardiac aspiration

200 mg/kg bw

      70 / m

survived

0.0

2.1

/

      88 / f

died

0.0

8.6

0.0

      12 / m

died

0.8

6.3

0.6

      24 / f

survived

0.9

3.1

/

      18 / f

died

0.6

2.9

0.1

      23 / f

survived

0.5

50.7

/

50 mg/kg bw

      82 / m

survived

0.0

1.6

/

      62 / f

survived

0.0

1.3

/

Applicant's summary and conclusion

Conclusions:
The oral LD50 for cat approximately amounts to 200 mg/kg bw. Lethality was not caused by MetHb formation.
Executive summary:

In order to assess the methemoglobin-forming potential of Acetessig-m-xylidid male and female cats received single oral doses of 50 or 200 mg/kg bw. Blood samples were taken before and after treatment.

In the high dose group cats showed apathy, salivation, ataxic gate, crying, prone position, lateral position, and decreased feed consumption. MetHb concentrations were slightly increased. 3 of 6 animals died.

In the low dose group no abnormalities were observed. MetHb concentration was very slightly increase. All animals survived.

Based on that the oral LD50 approximately amounts to 200 mg/kg bw. and lethality was not considered to be caused by MetHb formation.