Fenamiphos

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

May 12, 1981

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Fenamiphos

EC Number:

244-848-1

EC Name:

Fenamiphos

Cas Number:

22224-92-6

Molecular formula:

C13H22NO3PS

IUPAC Name:

{ethoxy[3-methyl-4-(methylsulfanyl)phenoxy]phosphoryl}(propan-2-yl)amine

Test material form:

solid: crystalline

Test animals

Species:

rat

Strain:

Wistar

Remarks:

SPF-bred Wistar rats of the strain Bor: WISW (SPF-Cpb)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann Experimental Animal Breeders in Borchen, Kreis Paderborn
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 11 weeks (males, females)
- Weight at study initiation: males 173 (163 -184) grams, the females of 183 (174 -191) grams
- Fasting period before study: yes, 18 h
- Housing: groups of 5 in Type III Makrolon® cages with low-dust wood pellets
- Historical data: available
- Diet (ad libitum): Altromin 1324 Maintenance Diet for Rats and Mice made by Altromin GmbH in Lage
- Water (ad libitum): tap water (watering bottles)
- Acclimation period:
- Microbiological status when known: SPF
- Method of randomisation in assigning animals to test and control groups: on the basis of randomizing lists generated by a program on an HP 3000 computer system

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

E 400

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

Doses:

1.0, 4.0, 5.0, 5.6, 6.3, 10.0, 100.00 mg/kg bw (males)
1.0, 5.0, 6.3, 8.0 mg/kg bw (females)

No. of animals per sex per dose:

5 animals/sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: prior to treatment and on days four, eight and 15
- Necropsy of survivors performed: yes
- Clinical signs: yes, recorded several times on the day of treatment, and at least once daily thereafter

Statistics:

If calculation of the mean (median) lethal dose (LD50) is possible, this operation is
performed with computer assistance (HP 3000) using the method of A.P. Rosiello, J.M.
Essigmann and G.N. Wogan (1977) as modified by Pauluhn (1983). This procedure is based on the "maximum likelihood" method of C.I. Bliss (1938). If pairs of results with 0 % and 100 % mortality exist, the geometric mean of the pertinent doses is considered the "approximate LD50".

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

6.1 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

6 mg/kg bw

Based on:

test mat.

Mortality:

Mortality was observed at and above 5.6 mg/kg bw in males and 5.0 mg/kg bw in females (please refer to "Any other information on results incl. tables").

Clinical signs:

other: other: see "Remark"

Gross pathology:

Lung: dark, patchy, distended, fluid, gray stipples; liver: dark, spleen: patchy, pale or dark; kidney: patchy; renal pelvis: reddened; grandular stomach: reddened, covered with ulcer-like foci; small intestine: slightly reddened, well supplied with blood.

Any other information on results incl. tables

Dose [mg/kg bw]	Toxicological results*			Duration of signs	Time of death	Mortality [%]
male rats
1.0	0	0	5	--	--	0
4.0	0	5	5	20m – 1d	--	0
5.0	0	5	5	17m – 1d	--	0
5.6	3	5	5	14m – 3d	25m – 1h15 m	60
6.3	4	5	5	12m – 1d	20m – 1h15m	80
10.0	4	5	5	18m – 1d	37m – 1h30m	80
100.0	5	5	5	6m – 8m	7m – 8m	100
female rats
1.0	0	5	5	4h45m – 1d	--	0
5.0	1	5	5	21m – 1d	49m	20
6.3	3	5	5	14m – 1d	34m – 1h15m	60
8.0	4	5	5	8m – 1d	20m – 34m	80
LD50 males: 6.0 mg/kg bw / LD50 females: 6.1 mg/kg bw

* 1^st figure = number of dead animals / 2^nd figure = number of animals with cinical signs / 3^rd figure = number of animals in the group

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

The test substance is very toxic to rats following acute oral administration. The oral LD50 of the test substance in rats was 6.0 – 6.1 mg/kg bw in males and females, respectively.

Executive summary:

A study for acute oral toxicity in rats was conducted with the test substance according to OECD 401 (adopted May 12, 1981). The test item was formulated with polyethylene glycol E 400. Groups of 5 male and 5 female rats were each administered by gavage a single dose of the test substance. The application volume was 5 mL/kg bw. The recovery period was 14 days. The animals were subjected to gross pathological examination after the recovery period.

Mortality was observed at and above 5.6 mg/kg bw in males and 5.0 mg/kg bw in females. Clinical signs (palmospasms, labored breathing, apathy, diarrhea, clonic craps, piloerection, issolated cases of spastic gait and bloody eyes) were recorded in all dose groups and animals, except for 1 mg/g bw in males. No adverse effects were observed in regard to the bodyweight. The gross necropsy revealed cahnges in the lung, liver, spleen, kidney, renal pelvis and small intestine.

It was concluded that the test substance is very toxic to rats following acute oral administration. The oral LD50 of the test subtance in rats was 6.0 – 6.1 mg/kg bw in males and females, respectively.