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Administrative data

Description of key information

oral: The LD50 for acute oral toxicity was 1400 mg/kg bw.

inhalation: The LD50 for acute inhalation toxicity was >4.66 mg/L air (highest attainable concentration)

dermal: The LD50 for acute dermal toxicity was >2000 mg/kg bw.

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:
10 February 1992 - 9 March 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Version / remarks:
EPA Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation:Human and Domestic Animals 81-1 Acute oral toxicity study (November 1984)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- batch No.of test material: 5007
- sample No.:1505E
- Expiration date of the lot/batch: March 1993

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 4°C in the dark




Species:
rat
Strain:
other: CD
Remarks:
of Sprague-Dawley origin (Hsd/Ola:Sprague-Dawley(CD))
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Ltd., Bicester,Oxon,England
- Age at study initiation: 6 weeks
- Weight at study initiation: 140 to 160 g
- Fasting period before study: yes
- Housing: in groups of 5 rats of the same sex in metal cages with wire mesh floors
- Diet: ad libitum, Standard laboratory diet (Biosure LAD 1)
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23°C
- Humidity (%): mean 58%
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
Preliminary study 800 mg/kg bw
Main study: 1000, 1260, 1600 mg/kg bw
No. of animals per sex per dose:
Preliminary study: 2/sex/dose
Main study: 5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
body weight: recorded on Day 1 (prior dosing), 8 and 15 or at death
animals were observed for clinical signs soon after dosing and at frequent intervals for the remainder of Day 1 and subsequent twice a day
- Macroscopic examination; macroscopic appearance of all examined tissues recorded

Statistics:
The acute median lethal oral dose (LD50) to rats was calculated using the method of Finney [FINNEY, D.J. (1971) Probit Analysis, 3rd ed., Cambridge University Press, Cambridge]. Separate LD50 values for males and females were estimated by undertaking probit analysis on the mortality data from the main study by fitting two parallel lines to the data (males only and females only) using the technique described by Finney [Finney, D.J. (1978) Statistical Method in Biological Assay, 3rd ed., Charles Griffin, London]. A chi-square test was carried out to check that the data did not contain any evidence of non-parallelism.
Preliminary study:
The results of the preliminary study indicated that the acute lethal oral dose to rats of MCPP-p 2EHE was greater than 0.8 g/kg bw.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 400 mg/kg bw
Based on:
test mat.
95% CL:
1.2 - 1.6
Sex:
male
Dose descriptor:
LD50
Effect level:
1 300 mg/kg bw
Based on:
test mat.
95% CL:
1.1 - 1.6
Sex:
female
Dose descriptor:
LD50
Effect level:
1 400 mg/kg bw
Based on:
test mat.
95% CL:
1.2 - 1.9
Mortality:
There were deaths following a single dose of MCPP-P 2-EHE among rats of both sexes dosed at 1260 mg/kg bw and above. Death occurred at intervals from Day 2 until Day 5.
Clinical signs:
Piloerection was observed in all rats within 5 minutes of dosing and throughout the remainder of Day 1. This sign persisted and was accompanied on Day 1 and/or later intervals by: abnormal body carriage (hunched posture), lethargy, decreased respiratory rate, ptosis, pallor of the extremities and ataxia for all rats dosedat 1000, 1260 and 1600 mg/kg bw; abnormal gait (waddling) for all rats dosed at 1000 and 1260 mg/kg bw and one male and one female dosed at 1600 mg/kg bw, prostration for two females dosed at 1000 mg/kg bw, four males and one female dosed at 1260 mg/kg bw and three males and three females dosed at 1600 mg/kg/bw. Recovery of surviving rats, as judged by external appearance and behavior, was complete by Day 4 (1260 mg/kg bw), Day 3 or 5 (1000 mg/kg bw) or Day 4 or 7 (1600 mg/kg bw).
Body weight:
Small bodyweight gains were recorded on Day 8 for one male and one female dosed at 1600 mg/kg bw and one female dosed at 1000 mg/kg bw. All other surviving rats achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No macroscopic abnormality was observed for animals killed on Day 15.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 for MCPP-P 2-EHE was 1400 mg/kg bw.
Executive summary:

A GLP study according EPA Pesticide Assessment Guidelines, 81-1 acute oral toxicity (Revised Edition November 1984) on rats was performed to assess the acute oral toxicity of MCPP-P 2-EHE. Groups of 10 fasted rats (5 male/5 female) were administered a single oral dose by gavage of the test substance, as supplied, at dose levels of 1000, 1260 and 1600 mg/kg bw. There were deaths among male and female rats dosed at 1260 mg/kg bw and above from Day 2 until Day 5. Clinical signs of reaction to treatment included pilo-erection, abnormal body carriage (hunted posture), abnormal gait (waddling), lethargy, decreased respiratory rate, ptosis, pallor of the extremities, ataxia and prostration. Recovery of surviving rats, as judged by external appearance and behavior, was complete by Day 4 (1260 mg/kg bw), Day 3 or 5 (1000 mg/kg bw) or day 4 to 7 (1600 mg/kg bw). Small bodyweight gains were recorded on Day 8 for one male and one female dosed at 1600 mg/kg bw and one female dosed at 1000 mg/kg bw. All other surviving animals achieved satisfactory bodyweight gains throughout the study. No abnormalities were recorded at macroscopic examination at the end of the study. The LD50 (males/females) was 1400 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 400 mg/kg bw
Quality of whole database:
GLP and Guideline study (EPA OPP 81-1)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 19, 1992 - September 9, 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OTS 798.1150 (Acute inhalation toxicity)
Qualifier:
according to guideline
Guideline:
other: EPA FIFRA 81-3
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
GLP compliance:
yes
Test type:
fixed concentration procedure
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- batch No.of test material: 5007
- sample No.:1505E
- Expiration date of the lot/batch: March 1993

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 4°C in the dark




Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK
- Age at study initiation: 6 weeks (male) and 8 weeks (female)
- Weight at study initiation: ca. 200 g
- Housing: stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C - 24°C
- Humidity (%): 25% - 65%
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
2.2 µm
Geometric standard deviation (GSD):
2.31
Remark on MMAD/GSD:
The proportion of droplets in the sub-micron size range was 17.8% and lower that EPA specification of 25%. Calculations show, that the 25% level was reached at a particle size of 1.23 µm.
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: aerosol generator; test substance was supplied from syringe driven at a constant rate by a syringe pump
- Exposure chamber volume: chamber with an internal volume of 120 L
- Method of holding animals in test chamber: chamber divided by wire mesh partitions to provide 10 separate animal compartments
- Source and rate of air: flow rate of 0.6 mL/min to give a concentration of 5 mg/L of air
- Temperature in air chamber:mean 23°C measured at the start and then at 30-minute intervals during exposure

TEST ATMOSPHERE
- analytical method used: HPLC
- Samples taken from breathing zone: yes, 5 samples during exposure


Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0 and 4.66 mg/L (highest achieved concentration)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: continuously during exposure and at least twice daily throughout the observation period; daily weighting from start until the end of the experiment
- Other examinations performed: food and water consumption was measured daily; macroscopic examination of all animals, lungs, liver and kidneys examined
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.66 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
One exposed female died overnight following exposure.
Clinical signs:
other: CLINICAL SIGNS. During exposure : signs consistent with exposure to an irritant aerosol, including partial closing of the eyes, wetness around the mouth and snout, and exaggerated respiratory movements. During observation period: signs seen in rats includ
Body weight:
Reduced bodyweight or reduced rate of bodyweight gain was evident for up to 5 days following exposure. Subsequently, weight gain was similar to that for control rats.
Gross pathology:
The lung weight to bodyweight ratio for the rat that died was higher than for the surviving rats.
Macroscopic pathology: the lungs of the rat that died following exposure the substance were congested and the stomach was gas-filled.
Other findings:
- Organ weights:
The lung weights were within normal limits for the control rats and for the surviving rats exposed to the test substance.. For the rat taht died the lung weight to bodyweight ratio was higher than for the surviving rats.

- Histopathology: The lungs of one rat exposed to the test substance were congested and the stomach was gas-filled. There were no abnormalities in any other rat.
Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 (4-hour) for MCPP-P 2-EHE is in excess of 4.66 mg/L. This was the highest attainable concentration.
Executive summary:

In a GLP study according to OECD 403, the acute inhalation toxicity of MCPP-P 2-EHE was assessed by exposing a group of rats to an aerosol produced from the test item. The control group was exposed to air only. The exposure duration was 4 hour in a whole body chamber followed by a 14-days observation period. The concentration of aerosol was measured during the exposure and the particle size distribution was assessed as well.

One female died following exposure and all animals showed signs of constant exposure to an irritant aerosol, including partial closing of the eyes, wetness around the mouth and snout and exaggerated respiratory movements. During the observation period, rats showed abnormal breathing, lethargy, wet fur, matted or oily fur and brown staining around the snout and jaws, but all surviving rats exposed to the test item were normal by day 8 of observation. The body weight was reduced for up to 5 days following exposure to MCPP-P 2-EHE but subsequently, weight gain was similar to that for control rats. Food consumption was reduced for up to one day following exposure and water consumption increased and remained high for several days following exposure to the test item. The lung weight to bodyweight ratios for rats surviving expose were within normal limits.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
4 660 mg/m³
Quality of whole database:
GLP and Guideline Study (OECD TG 403)

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:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Version / remarks:
EPA Pesticide Assessment Guidelines, Subdivision F. Hazard Evaluation:Human and Domestic Animals 81-2 Acute dermal toxicity study, revised edition November 1984
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- batch No.of test material: 5007
- sample No.:1505E
- Expiration date of the lot/batch: March 1993

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 4°C in the dark




Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Froxfield (U.K.) Ltd., Petersfield, Hampshire, England
- Age at study initiation: 9 to 14 weeks
- Weight at study initiation: 2.2 to 2.9 kg
- Fasting period before study:
- Housing:
- Diet: ad libitum, Standard Laboratory Diet (SDS Rabbit Diet SQC)
- Water: ad libitum
- Acclimation period: 7days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21°C
- Humidity (%): mean 53%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: hair was clipped one day prior treatment, application on 50 mm x 50 mm area on dorso-lumbar region
- % coverage: 10% of total body surface
- Type of wrap if used: treated area covered promptly with gauze, which was held in place with an impermeable dressing encircled firmly around the trunk
REMOVAL OF TEST SUBSTANCE
- Washing: at the end of exposure; with warm (30-40°C) water and blotted dry with absorbent paper
- Time after start of exposure: 24 hours
A Perspex `Elizabethan´ collar was then fitted to each animal for the remainder of the experimental day to minimize oral ingestion of residual test substance.
TEST MATERIAL
- Amount(s) applied: 2000 mg/kg bw
- Constant volume or concentration used: yes


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:
. twice daily checked for mortalities
. on Day 1 after dosing and at frequent intervals checked for clinical signs, subsequent twice daily
- bodyweight: recorded on Day 1, 8 and 15, individual bodyweight chances were caluculated weekly.
-macroscopic examination: macroscoupc appearance of all examined tissues was recorded at the end of the experiment
- Dermal responses: Local dermal irritaion at the treatment site was assessed daily using the following numerical system:

No erythema 0
Slight erythrema 1
Well-defined erythema 2
Moderate erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Oedema formation:

No oedema 0
slight oedema 1
Well-defined oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths following a single dermal application of MCPP-P 2-EHE at 2000 mg/kg bw.
Clinical signs:
There were no clinical signs of reaction to treatment.
Body weight:
All rabbits achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Terminal examination revealed white foci (up to 3 mm in diameter, extending into the parenchyma or seen on the cut surface of the tissue) on the liver capsular region of all rabbits.
Other findings:
Dermal responses:Slight erythema accompanied by slight edema was recorded at the sites of application of MCPP-P 2-EHE on Day 2. These reactions persisted throughout the first week of the study. Irritation had resolved for the majority of animals by Day 9 although reactions continued for one male until Day 12.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 for MCPP-P 2EHE is greater than 2000 mg/kg bw.
Executive summary:

A limit test to assess the acute dermal toxicity of MCPP-P 2-EHE on rabbit skin was performed according to EPA Pesticide Assessment Guidelines, 81-2 acute dermal toxicity (Revised Edition November 1984). The test item was applied undiluted on clipped skin of 5 male and 5 female rabbits at a dose level of 2000 mg/kg bw for an observation period of 14 days. There were no deaths and no clinical signs of reaction to treatment and normal body weight gain during the study. Slight erythema and edema was recorded at the sites of application on Day 2. Dermal irritation persisted throughout the first week of the study. Irritation had resolved by Day 8 or 9 for the majority of animals and Day 13 for one animal. Macroscopic examinations revealed white foci on the liver capsular region of all rabbits. The LD50 of MCPP-P 2-EHE was found to be greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP and Guideline study (EPA OPP 81-2)

Additional information

oral

A GLP study according EPA Pesticide Assessment Guidelines, 81 -1 acute oral toxicity (Revised Edition November 1984) on rats was performed to assess the acute oral toxicity of MCPP-P 2-EHE. Groups of 10 fasted rats (5 male/5 female) were administered a single oral dose by gavage of the test substance, as supplied, at dose levels of 1000, 1260 and 1600 mg/kg bw. There were deaths among male and female rats dosed at 1260 mg/kg bw and above from Day 2 until Day 5. Clinical signs of reaction to treatment included pilo-erection, abnormal body carriage (hunted posture), abnormal gait (waddling), lethargy, decreased respiratory rate, ptosis, pallor of the extremities, ataxia and prostration. Recovery of surviving rats, as judged by external appearance and behavior, was complete by Day 4 (1260 mg/kg bw), Day 3 or 5 (1000 mg/kg bw) or Day 4 to 7 (1600 mg/kg bw). Small bodyweight gains were recorded on Day 8 for one male and one female dosed at 1600 mg/kg bw and one female dosed at 1000 mg/kg bw. All other surviving animals achieved satisfactory bodyweight gains throughout the study. No abnormalities were recorded at macroscopic examination at the end of the study. The LD50 (males/females) was 1400 mg/kg bw (MCPP-p Task Force 920497D/JEL 47/AC;1992).

inhalation

In a GLP study according to OECD 403, the acute inhalation toxicity of MCPP-P 2-EHE was assessed by exposing a group of rats to an aerosol produced from the test item. The control group was exposed to air only. The exposure duration was 4 hour in a whole body chamber followed by a 14-days observation period. The concentration of aerosol was measured during the exposure and the particle size distribution was assessed as well. One female died following exposure and all animals showed signs of constant exposure to an irritant aerosol, including partial closing of the eyes, wetness around the mouth and snout and exaggerated respiratory movements. During the observation period, rats showed abnormal breathing, lethargy, wet fur, matted or oily fur and brown staining around the snout and jaws, but all surviving rats exposed to the test item were normal by day 8 of observation. The body weight was reduced for up to 5 days following exposure to MCPP-P 2-EHE but subsequently, weight gain was similar to that for control rats. Food consumption was reduced for up to one day following exposure and water consumption increased and remained high for several days following exposure to the test item. The lung weight to bodyweight ratios for rats surviving expose were within normal limits. The discriminating dose for MCPP-P 2-EHE is in excess of 4.66 mg/L, which was the highest attainable concentration (MCPP-p Task Force JEL 68/930510; 1993).

dermal

A limit test to assess the acute dermal toxicity of MCPP-P 2-EHE on rabbit skin was performed according to EPA Pesticide Assessment Guidelines, 81-2 acute dermal toxicity (Revised Edition November 1984). The test item was applied undiluted on clipped skin of 5 male and 5 female rabbits at a dose level of 2000 mg/kg bw for an observation period of 14 days. There were no deaths and no clinical signs of reaction to treatment and normal body weight gain during the study. Slight erythema and edema was recorded at the sites of application on Day 2. Dermal irritation persisted throughout the first week of the study. Irritation had resolved by Day 8 or 9 for the majority of animals and Day 13 for one animal. Macroscopic examinations revealed white foci on the liver capsular region of all rabbits. The LD50 of MCPP-P 2-EHE was found to be greater than 2000 mg/kg bw (MCPP-p Task Force 920469D/JEL 49/AC; 1992).

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The oral LD50 was 1400 mg/kg bw. As a result the substance is classified for acute oral toxicity (Cat.4, H302:" Harmful if swallowed") under Regulation (EC) No 1272/2008,as amended for the tenth time in Regulation (EU) No 2017/776. Classification for acute dermal and inhalation toxicity is not warranted.