Octyl (R)-2-(4-chloro-2-methylphenoxy)propionate

Endpoint summary

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(2001)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: HsdCpb:Wu
- Source: Harlan GmbH, 5960 AD Horst, Netherlands
- Age at study initiation: approximately 8-12 weeks
- Weight at study initiation: 161-198 g
- Fasting period before study: Food was withheld from the animals for approximately 16-24 h before administration of the test item, and they were fed again approximately 2-4 h after administration.
- Housing: The animals were group caged conventionally in polycarbonate cages on low dust wood granulate bedding.
- Diet and water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Administration volume: 10 mL/kg bw

Doses:

2000 mg/kg bw , 300 mg/kg bw

No. of animals per sex per dose:

6 (3 animals per step)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs and mortality rates were determined several times on the day of administration and subsequently at least once daily. The weight gain was checked weekly until the end of the study.
- Necropsy of survivors performed: yes

Statistics:

The LD50 value was estimated according to OECD TG 423, Annex 2d (2001).

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Remarks on result:

other: LD50 cut off according OECD TG 423, Annex 2d

Mortality:

3 deaths at 2000 mg/kg, no deaths at 300 mg/kg (1st and 2nd step)

Clinical signs:

other: The following clinical signs were observed in animals dosed with 2000 mg/kg bw: poor reflexes, decreased reactivity, lateral position and laboured breathing. In animals dosed with 300 mg/kg bw no clinical signs were observed.

Gross pathology:

In animals treated with 2000 mg/kg bw that died during the observation period a black, spotted liver was detected. The necropsies performed at the end of the study revealed no particular findings in animals treated with 300 mg/kg bw.

Executive summary:

An acute oral toxicity study according to OECD TG 423 (Acute Toxic Class Method) was conducted with a starting dose of 2000 mg/kg test item formulated in corn oil. As 100% mortality occurred for this dose the next lower dose (300 mg/kg) was employed. No mortalities occurred for this dose neither in the 1st nor in the 2nd step. Thus, according to OECD TG 423, Annex 2d, the LD50 cut off is 500 mg/kg for Mecoprop-P n-octyl ester.

For the rats of dose group 2000 mg/kg poor reflexes, decreased reactivity, lateral position and laboured breathing were observed. At necropsy a black spotted liver was detected for the same dose level. For the 300 mg/kg dose level no clinical signs, effects on body weight gain or gross pathology findings were reported.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

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: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1987)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: HsdCpb: Wu
- Source: Harlan GmbH, 5960 AD Horst, Netherlands
- Age at study initiation: approximately 9-13 weeks
- Weight at study initiation: males 287-300 g; females 243-253 g
- Housing: The animals were caged individually in polycarbonate cages on low dust wood granulate bedding.
- Diet and water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
One day before the start of the treatment the back and flanks of the rats were shorn (approximately 10% of the body surface area). For each dose and animal the required amount of the pure liquid test substance was calculated on the base of the body weight at time of dosing. This amount was weighed and applied as uniformly and thinly as possible to the test area, covered with a gauze-layer (6.0 cm x 5.0 cm = 30.0 cm²) of a "Cutiplast steril" coated with "Leukoflex". The gauze strip was placed on the rat's back and secured with a "Lomir biomedical Inc rat jacket", which was connected with a safety pin to the stretch tape to ensure that the animals could not ingest the test substance.

REMOVAL OF TEST SUBSTANCE
After approximately 24 hours the dressings were removed and the area was rinsed with tepid water using soap and gently patting the area dry.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw per 30.0 cm²
Dose range: males 19.1 - 20.0 mg/cm²; females 16.2 - 16.9 mg/cm².

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: at least 14 days
- Frequency of observations and weighing: Clinical signs and mortality rates were determined several times on the day of application and subsequently at least once daily. The weight gain of the animals was checked weekly until the end of the study.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortalities occurred.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

The necropsies performed at the end of the study revealed no particular findings.

Executive summary:

An acute dermal toxicity study with Mecoprop-P n-octyl ester was conducted according to OECD TG 402.

For the purpose of a limit test 2000 mg/kg of the test item were applied semiocclusive on 5 male and 5 female rats for 24 hours. No mortalities, no clinical signs, no effects on weight development and no gross pathological findings were observed during the 14 -day observation period.

The resulting LD50 for Mecoprop-P n-octyl ester was therefore > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

An acute oral toxicity study with Mecoprop-P n-octyl ester according to the Acute Toxic Class Method (OECD TG 423) was conducted with a starting dose of 2000 mg/kg formulated in corn oil. As 100% mortality occurred for this dose the next lower dose (300 mg/kg) was employed. No mortalities occurred for this dose neither in the 1st nor in the 2nd step. Thus, the LD50 cut off according to OECD TG 423, Annex 2d, is 500 mg/kg for Mecoprop-P n-octyl ester.

For the rats of dose group 2000 mg/kg poor reflexes, decreased reactivity, lateral position and laboured breathing were observed. At necropsy a black spotted liver was detected at this dose level. For the 300 mg/kg dose level no clinical signs, effects on body weight gain or gross pathology findings were reported.

 

An acute dermal toxicity study with Mecoprop-P n-octyl ester according to OECD TG 402 with a limit dose of 2000 mg/kg revealed no mortalities, no clinical signs, no effects on body weight development and no gross pathological findings.

The resulting LD50 for Mecoprop-P n-octyl ester was therefore > 2000 mg/kg bw.

 

No experimental studies on acute inhalation toxicity are available for Mecoprop-P n-octyl ester, but for the structural analogue Mecoprop-P 2-ethylhexyl ester (MCPP-P 2-EHE) and Mecoprop-P acid (MCPP-P acid), which is the hydrolysis product of Mecoprop-P octyl ester and MCPP-P 2-EHE.

Evidence exists that systemic toxicity is similar for the three substances with respect to dose level and target organ. This is based on the fact that the esters are in vivo rapidly metabolised to Mecoprop-P acid (MCPP-P acid) and the corresponding alcohols, and thus systemic toxicity is finally determined by the same species.

 

A full and elaborated justification for the read-across is attached to this endpoint summary, showing that grouping and read across is warranted for systemic toxicity. With regard to local effects (e.g. on respiratory tract) read-across cannot be applied per se, because the substances belong to different chemical classes, i.e. ester and acid, and, at least for the acid a higher irritating potential might be assumed. However, both studies on acute inhalation toxicity reveal comparable LC50 (4h) of > 4.66 mg/L (highest attainable concentration) and > 5.6 mg/L, for the ester and the acid respectively. Thus, using the available data of Mecoprop-P 2–EHE and Mecoprop-P acid, acute inhalation toxicity is assumed to be low for Mecoprop-P n-octyl ester.

Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for selection of acute toxicity – inhalation endpoint
According to REACH (Regulation (EC) 1907/2006), Annex VIII, acute toxicity studies for two appropriate exposure routes are a standard information requirement. The relevant exposure routes are for the substance by oral and dermal route. Thus, a study on acute inhalation toxicity is no REACH requirement. Nevertheless, read across indicates low acute inhalation toxicity for the substance.

Justification for selection of acute toxicity – dermal endpoint
Only one study available

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008, Annex I, a classification as Acute Tox. 4 (H302: Harmful if swallowed) is warranted.