Allyl phenoxyacetate

Endpoint summary

Description of key information

Oral (OECD 401), rat: LD50 = 835 mg/kg bw
Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw (limit test)

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:

June - July 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

No information on purity was given.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

Deviations:

yes

Remarks:

No information on purity was given.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 109 - 117 g (males), 103 - 116 g (females)
- Fasting period before study: overnight prior to dosing
- Housing: individually in solid-bottom polypropylene boxes, softwood sawdust was used as bedding material
- Diet: R 4 Alleindiät für Ratten (Ssniff Versuchstier-GmbH, Soest, Germany), ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 40% alcohol pure in polyethyleneglycol 200 (v/v)

Details on oral exposure:

A range-finding study was carried out to establish a dosing regimen for the main study.

VEHICLE
- Concentration in vehicle: range-finding study: 25, 50, 200 and 500 mg/mL; main study: 50, 63, 79.4 and 100 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

Range-finding study: 250, 500, 2000 and 5000 mg/kg bw
Main study: 500, 630, 794 and 1000 mg/kg bw

No. of animals per sex per dose:

Range-finding study: 2 males and 2 females
Main study: 5 males and 5 females

Control animals:

no

Details on study design:

Range-finding study:
- Duration of observation period following administration: 7 days
- Frequency of observations: Animals were observed daily during the 7 day period following treatment. Individual body weights were recorded on the day of treatment.
- Necropsy of survivors performed: no

Main study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 15 and 30 min and 1, 2 and 4 h after administration and subsequently at least once daily for 14 days. Individual body weights were determined on the day before treatment (Day -1), on the day of treatment (Day 0), at death and again 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

The acute oral median lethal dose LD50 and 95% fiducial limits for combined male and female animals were calculated using probit method (Finney, D.J. (1964), Statistical Methods for Biological Assay, 2nd Edition, London, Charles Griffin).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

835 mg/kg bw

Based on:

test mat.

95% CL:

> 716 - < 974

Mortality:

Range-finding study: All animals died at 2000 and 5000 mg/kg bw. No mortality was observed at 250 and 500 mg/kg bw. The mortalities indicated a LD50 in the range of 500 - 2000 mg/kg bw.

Main study: Three males and four females died at 1000 mg/kg bw, one male and 3 females at 794 mg/kg bw and 3 males at 630 mg/kg bw. With exception of one animal which died on Day 4 after treatment, all animals were found dead 4 h up to 2 days after treatment. No mortality occurred at 500 mg/kg bw.

Clinical signs:

other: The majority of animals showed lacrimation, piloerection, hunched position, oscillated movements and shaggy coat following treatment in all dose level groups. Other occasional signs of intoxication were lethargy at 630 mg/kg bw and higher, eyes half close

Gross pathology:

Sacrificed animals:
Thickened areas covering partially the mucosal surface of the forestomach and adhesions:
a) between forestomach and liver
b) between forestomach, liver and spleen
c) between forestomach, liver, spleen and peritoneum

Dead animals:
Macroscopic findings were mainly associated with the gastrointestinal tract. The following toxic abnormalities were observed:
Stomach overloaded, severe reddening of the forestomach, red patches on mucosal surface of corpus and anteum of stomach. Moderate until severe congestion in liver, presence of bloody fluid in thorax and rounded spot of blood on the surface of thyme.
Additional observations were noted in one animal that died 4 days after treatment: false membrane, thickness and red patches in the mucosal surface of the forestomach, slight adhesion between forestomach and spleen and loamy-coloured liver.

Table 1. Results of the acute toxicity study.

Dose level (mg/kg bw)	Mortalities
	Male	Female
500	0/5	0/5
630	3/5	0/5
794	1/5	3/5
1000	3/5	4/5

Interpretation of results:

other: Acute Tox. Cat. 4 according to Regulation (EC) No 1272/2008

Conclusions:

In this acute oral toxicity study a LD50 value of 835 mg/kg bw in male and female rats was calculated according to the method of Finney (1963).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

835 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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

Study period:

Mar 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Non-GLP study performed acccording to guidelines of the USA Interagency Regulatory Liaison Group (IRLG) Testing Standards and Guidelines Work Group (January 1981). No information on purity was given; occlusive application

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

The skin was abraded prior to treatment; occlusive application; No information on purity was given.

GLP compliance:

no

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
- Age at study initiation: 7-11 weeks
- Weight at study initiation: 225-240 g (males), 205-220 g (females)
- Fasting period before study: overnight prior to dosing
- Housing: individually in solid-bottom polypropylene boxes, softwood sawdust was used as bedding material
- Diet: R 4 Alleindiät für Ratten (Ssniff Versuchstier-GmbH, Soest, Germany), ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 40-70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: 10%
- Type of wrap if used: The treated skin was covered with a porous gauze dressing and occluded with a strip of impermeable adhesive plaster wound around the trunk.
The application site was abraded using a sterile clipper head immediately prior to treatment.

REMOVAL OF TEST SUBSTANCE
- Washing: The skin and surrounding areas were wiped with a moist disposable towel to remove any residual test substance.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amounts applied: 1.7 mL/kg bw
- Constant concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 15 and 30 min and 1, 2 and 4 h after administration and subsequently once daily for 14 days. Individual body weights were determined on day before treatment (Day -1), on the day of treatment (Day 0) and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: histopathological examination of the kidney, liver and (treated) skin tissue of 3 males and 3 females

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period of the main study.

Clinical signs:

other: Clinical changes like lacrimation, half-closed eyes, soft faeces and exophthalmia were observed on the application day. All animals appeared normal on Day 2 after treatment.

Gross pathology:

No significant pathological changes were found.

Other findings:

- Histopathology: liver: small intralobular/periportal infiltrates of round cells and congestion; kidneys: focal, subacute, interstitial nephritis in the cortex, focal proliferation of epithelial cells in the renal tubules and small interstitial infiltrates of round cells in the cortex; skin: slight hyperkeratosis

Details on test animals:

- Source: Charles River Wiga GmbH, Sulzfeld, Germany

The abraded skin of all animals appeared normal throughout the study period.

Histopathological examination revealed small intralobular/periportal infiltrates of round cells and congestion in the liver. In the kidneys, focal subacute, interstitial nephritis in the cortex, focal proliferation of epithelial cells in the renal tubules and small interstitial infiltrates of round cells in the cortex were observed. Furthermore, slight hyperkeratosis was found in skin tissues.

Evaluation of the histopathological findings:

A slight hyperkeratosis of the skin is an indication for minimal irritation on the application site. Small infiltrates of round cells in liver and kidneys as well as a slight focal interstitial nephritis are indications for small local infections as they can frequently be found in rats under conventional husbandry. In that connection, small focal proliferates of epithelial cells in the renal tubules were also found. The congestion is conditioned by the fact that the animals were not exsanguinated.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

In this acute dermal toxicity study a LD50 value > 2000 mg/kg bw in male and female rats was found.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Oral

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 401 (1982). In a dose range-finding study 2 male and 2 female rats per dose group were administered 250, 500, 2000 and 5000 mg/kg bw of the test substance. All animals died at 2000 and 5000 mg/kg bw. No mortality was observed at 250 and 500 mg/kg bw.

Based on the results from the dose range-finding study, 5 male and 5 female rats per dose group were administered the test substance at doses of 500, 630, 794 and 1000 mg/kg bw. Animals were observed 15 and 30 min and 1, 2 and 4 h after dosing and subsequently at least once daily for 14 days. Individual body weights were recorded on the day before treatment (Day -1), on the day of treatment (Day 0), and again 7 and 14 days after treatment at death. Macroscopic examination was performed at the end of the observation period at terminal sacrifice. Three males and four females died at 1000 mg/kg bw, one male and 3 females at 794 mg/kg bw and 3 males at 630 mg/kg bw. With exception of one animal which died on Day 4 after treatment, all animals were found dead 4 h up to 2 days after treatment. No mortality occurred at 500 mg/kg bw. The majority of animals showed lacrimation, piloerection, hunched position, oscillated movements and shaggy coat following treatment in all dose groups. Other signs of systemic toxicity were lethargy starting at 630 mg/kg bw, eyes half closed, hyperthermia and difficult breathing at 794 and 1000 mg/kg bw. All surviving animals appeared normal on Day 4. All surviving animals showed acceptable body weight gain at the end of the observation period. Abnormalities noted at necropsy of animals that died during the study were mainly associated with the gastrointestinal tract. Abnormalities such as overloaded stomach, severe reddening of the forestomach, red patches on mucosal surface of the corpus and antrum of the stomach were observed. Furthermore, moderate to severe congestion in the liver and presence of bloody fluid in the thorax were noted. Additional observations were noted in one animal that died 4 days after treatment. Abnormalities noted in surviving animals were thickened areas covering partially the mucosal surface of the forestomach and adhesions between a) forestomach and liver, b) forestomach, liver and spleen, c) forestomach, liver, spleen and peritoneum. Based on the results of this study, the LD50 value was determined to be 835 mg/kg bw in rats.

 

Dermal

The acute dermal toxicity of the test substance was assessed in a limit test performed in 5 male and 5 female SD rats according to OECD Guideline 402 and in compliance with GLP (1983). A single dose of 2000 mg/kg bw of the test substance was applied uniformly over an area of approximately 10% of the total body surface to the abraded skin of rats under occlusive conditions for 24 hours. Animals were inspected for deaths or overt signs of toxicity 15 and 30 min and 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded on the day before treatment (Day -1), on the day of treatment (Day 0), and again 7 and 14 days after treatment at death. Individual skin reactions were assessed and graded at the application site 24.5 (nominally 24) h after treatment and daily until the end of the observation period. Macroscopic examination was performed at the end of the observation period at terminal sacrifice. Additionally, a histopathological examination of the kidney, liver and treated skin tissue from 3 males and 3 females was performed. There was no mortality and no effects on body weight gain during the 14-day observation period. Clinical signs such as lacrimation, half-closed eyes, soft faeces and exophthalmia were observed on the application day. All animals appeared normal on Day 2 after treatment. The abraded skin of all animals appeared normal throughout the study period. No abnormalities were noted at necropsy. Histopathological examination revealed small intralobular/periportal infiltrates of round cells and congestion in the liver. In the kidneys, focal subacute, interstitial nephritis in the cortex, focal proliferation of epithelial cells in the renal tubules and small interstitial infiltrates of round cells in the cortex were observed. Furthermore, slight hyperkeratosis was found in skin tissues. The LD50 value for dermal toxicity is considered to be > 2000 mg/kg bw.

Justification for classification or non-classification

The available data on acute oral toxicity of the test substance meet the criteria for Acute Tox. Cat 4 (H302) according to Regulation (EC) 1272/2008.

The available data on acute dermal toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.