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Administrative data

Description of key information

oral
rat: LD50 > 5000 mg/kg bw; transient clinical signs (OECD 401; BASF AG 1986)
rat: LD50 > 5000 mg/kg bw; reduced bw in females (GLP, OECD 401; Rohm & Haas 2002)
rat: LD50 > 2000 mg/kg bw; no clinical signs (GLP, OECD 423; BSL 2000)
inhalation
no data available
dermal
rat: LD50 > 5000 mg/kg bw (GLP, OECD 402; Rohm & Haas 2002)
rabbit: LD > 5000 mg/kg bw (Rohm & Haas 1977, 1976)

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:
2000-09-18 to 200-10-13
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:
22 March 1996
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
Directive 96/54/EEC
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Weight at study initiation: males: 150 g +/- 20 %; females: 150 g +/- 20 %
- Fasting period before study: over night
- Housing: animals were kept in Macrolon cages on Altromin saw fiber bedding
- Diet: Altromin 1324 maintenance diet for rats and mice, totally-pathogen-free (TPF), feeding at libitum
- Water: Free access to tap water (drinking water, municipal residue control, microbiol. controlled periodically)
- Acclimation period: Adequate acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 55 ± 10 %
- Air changes: 10 x / hour
- Photoperiod: Artificial light, lighting regime 12 : 12 hours, light 6.00 - 18.00

IN-LIFE DATES: From:2000-09-26 To: 2000-10-12
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4000 mg of test item (50 % in water) were solved in 1 % conc. ad 10 mL
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: The vehicle was chosen due to its non-toxic characteristics.
- Lot/batch no.: CMC, Sigma, Lot-No. 36H0738


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test substance was freshly mixed prior to application and stirred throughout dose administration to guarantee stability and homogenicity.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 males/3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: Animals were observed for 14 days after dosing.
- Frequency of observations and weighing: The animals were weighed prior to first application and once a week thereafter.
- Necropsy of survivors performed: At the end of the observation period the animals were sacrificed by an overdosage of pentobarbital.
All animals were subjected to gross necropsy. All gross pathological changes were recorded.
- Other examinations performed: A careful clinical examination was made twice a day on the day of dosing and once a day thereafter.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No compound related mortality was observed.
Clinical signs:
No clinical signs of toxicity were observed throughout the observation period.
Body weight:
Throughout the 14-days observation period no weight loss was recorded. The weight gain for the male and female animals was within the expected range.
Gross pathology:
Necropsy revealed an acute injection of blood vessels in all animals in the abdominal region. This finding is due to euthanasia with an overdose of pentobarbital injected intraperitoneally.
No other macroscopic necropsy findings were recorded.
Other findings:
No other macroscopic necropsy findings were recorded.
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.

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:
2001-08-22 to 2001-09-05
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)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
92/69/EEC
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japan 59 NohSan Notification No. 4200, Acute Dermal Toxicity Study
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl CD BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC.
- Age at study initiation: Females were approximately 9 weeks old and males were 8 weeks old.
- Weight at study initiation: The body weights ranged from 258 to 275 g for males and from 203 to 241 for females.
- Fasting period before study:
- Housing: The animals were individually housed in suspended stainless steel cages (18x34~20c m) with wire mesh fronts and bottoms. Cages were suspended above absorbent-paper pan liners which were changed 3 times a week.
- Diet: Throughout the test period, all rats had free access to PMI Certified Rodent Diet 5002(C) (Purina Mills Inc., Richmond, IN).
- Water: Throughout the test period, all rats had free access to water (via automatic watering) purified by reverse osmosis.
- Acclimation period: approximately one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 46-58
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: entire trunk between flank and shoulders; intact skin
- % coverage: approx. 6*6 cm (10% of the body surface area (target))
- Type of wrap if used: Polyethylene sheet covered with Elastoplast elastic bandages and secured in place with adhesive tape.


REMOVAL OF TEST SUBSTANCE
- Washing: After the 24-hr exposure, the application sites were wiped with paper towels saturated with tap water and blotted dry with paper towels.
Duration of exposure:
24 h
Doses:
5000 mg/kg bw. The dose was calculated on an "as is" basis; no adjustment was made for percent active ingredient.
No. of animals per sex per dose:
5
Control animals:
other: Historical data were used for weight controls.
Details on study design:
All animals were observed for signs of ill health, or reaction to treatment at approximately 1, 2 and 4 hrs after dosing and once daily thereafter for 14 days. Body weights were recorded on day 0 (prior to dosing) and on days 7 and 14. Surviving rats were euthanized on day 14 and necropsied. Necropsy consisted of a gross examination of organs in situ.
Statistics:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
- Time of death: No mortality was observed.
- Number of deaths at each dose: No mortality was observed.
Clinical signs:
Scant feces was observed in 2 females on a single day during the observation period. Periodically during the study, the fur surrounding the eyes and muzzle of several animals was observed to be red stained; these effects were judged to be caused by the occluded testing methodology and by the use of collars.
Body weight:
There were no treatment-related body weight effects when compared to historical control data.
Gross pathology:
No gross changes.
Other findings:
LOCAL FINDINGS
Signs of skin irritation including edema, erythema and desiccation was observed beginning day 1 of the observation period and continuing through day 11.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
GLP and guideline study

Additional information

There are reliable data available to assess the acute oral and dermal toxicity of ureido methacrylate.

Oral

Results of a few studies indicate a very low acute toxic potential of ureido methacrylate for rats after oral application. In the most reliable studies performed according to OECD test guideline 401, the LD50 values were > 5000 mg/kg bw after 14 days of observation. No substance related mortality was observed in the study performed by BASF AG (1986); clinical signs (dyspnoea, apathy, poor general state, staggering and imbalance) were observed directly after administration of the test substance (purity > 99%). In a GLP conform limit test, no mortality was observed and reduced body weight gain in female rats (-26%) was observed as sign of toxicity after administration of the test substance (purity unknown; Rohm & Haas 2002).

In a study according to OECD guideline 423, the test item ureido methacrylate was given in a dose of 2000 mg active ingredient/kg body weight to two groups of 3 male and 3 female rats (Wistar) in a single exposure via oral gavage. A careful clinical examination was made once a day. At the end of the observation period the animals were sacrificed and necropsy was carried out to record gross pathological changes. A maximum dosage of 2000 mg/kg bw according to the acute toxic class method regime, caused no compound related mortality within 14 days post application.. No clinical signs of toxicity were observed throughout the observation period. The LD50 was determined to be > 2000 mg/kg BW.(BSL, 2000)

Inhalation

In accordance with column 2 of REACH Annex VIII, the test acute toxicity after inhalation (required in section 8.5) does not need to be conducted as acute toxicity studies for oral and dermal application are available. Inhalation exposure is regarded negligible as the vapour pressure of the substance is very low. In addition, inhalation is a unlikely route of human exposure for this substance.

Dermal

Ureido methacrylate showed a very low acute toxic potential in rats and rabbits after dermal application in a few studies performed by Rohm & Haas. In the most reliable study performed according to GLP requirements and OECD test guideline 402, the acute dermal toxicity of ureido methacylate (containing approximately 50% active ingredient) was assessed in Crl: CD®BR rats. The test substance was applied to the shaved intact skin of five male and five female rats at 5000 mg/kg body weight. The application sites were occluded for 24 hrs. After the 24-hr exposure, the application sites were wiped with paper towels saturated with tap water and blotted dry with paper towels. There were no mortalities or body weight effects. Scant feces were observed in 2 females on a single day during the observation period. Signs of skin irritation including edema, erythema and desiccation were observed beginning day 1 of the observation period and continuing through day 11. Necropsy revealed no gross changes. The acute dermal LD50 for ureido methacrylate was greater than 5000 mg/kg in male and female rats.

Comparable results were provided by two rabbit studies with limited documentation (Rohm & Haas 1977, 1976). In rabbits no local irritant effects were observed if the test substance did not adhered to the skin; then well-defined erythema were identified (edema could not properly estimated; Rohm & Haas 1977).


Justification for selection of acute toxicity – oral endpoint
The most reliable study was selected. Study was conducted in compliance with guideline and GLP regulation.

Justification for selection of acute toxicity – inhalation endpoint
Exposure via inhalation is not considered relevant, due to unlikely exposure via inhalation route.

Justification for selection of acute toxicity – dermal endpoint
The most reliable study was selected. Study was conducted in compliance with guideline and GLP regulation.

Justification for classification or non-classification

Ureido methacrylate showed a very low toxic potential after single oral or dermal application. A classification is therefore not warranted accoding to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (GHS, CLP).

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