Formaldehyde, polymer with benzenamine, hydrogenated

Endpoint summary

Description of key information

Based on the key study, the oral LD50 of the test substance in rats is > 50 - 300 mg/kg (Evonik_Stockhausen, 2005).

The dermal LD50 in rabbits is >700 mg/kg (no deaths were observed, but necrotic skin and severe edema was noted in males and females). 

Testing for dermal toxicity at higher doses is not warranted as the material is corrosive to the skin.

No data is available regarding acute inhalation toxicity. A data waiver is claimed.

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:

2005-02-14 to 2005-03-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2001)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(2004)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: White Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: 
- Source: White WISTAR, Harlan Winkelmann, Borchen, Germany
- Weight at study initiation: 165.2 - 199.0 g, about 9 weeks
- Fasting period before study: maximum 20 hours
- Diet: Altromin, rat diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
- Temperature (°C): 22 °C +/- 3° C
- Humidity (%): 30 % - 70 %
- Air changes (per hr): 8 times
- Illumination: 12 hours artifical fluorescent light and 12 hours dark

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

ADMINISTRATION: 
- Frequency: single dosage on day 1
- Dose: 300 mg/kg/bw (applied as 10 % w/w) and 50 mg/kg bw (applied as 5 % w/w)
- DOSAGE PREPARATION: dispersion in sesame oil
- Starting dose 300 mg/kg bw, next step 50 mg/kg bw

Doses:

300 mg/kg/bw and 50 mg/kg bw

No. of animals per sex per dose:

3 female at 300 mg/kg
6 female at 50 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: periodic intervals on the dayof dosing and once daily thereafter, until day 15
- Body weight: days 1 (pre-administration) 8 and 15
- Necropsy: Animals died ahead of schedule were necropsied immediately, all survived animals were necropsied at the end of the observation period

Statistics:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Mortality:

300 mg/kg: 2 of 3 female rats died within 20 minutes after application
50 mg/kg: no mortality

Clinical signs:

other: 300 mg/kg: 2 of 3 female rats showed ataxia, decreased respiration, gasping, side position and convulsion, died within 20 minutes after application 50 mg/kg: no toxic symptoms were observed

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Other findings:

no other findings

no other information

Conclusions:

The LD50 cut-off for VESTAMIN EP-HS 10 was estimated to be 300 mg/kg. Ranking of the test substance VESTAMIN EP-HS 10 according to the Global Harmonised System resulted in Category 3: > 50 - 300 mg/kg

Executive summary:

The acute oral toxicity study of VESTAMIN EP-HS 10 was determined with 9 female WISTAR rats. Animals were observed for symptoms of clinical toxicity and mortality for 14 days after treatment. At first 3 female rats were treated with 300 mg/kg bw. Two rats showed ataxia, decreased respiration, gasping, side position and convulsion and died within 20 minutes after application. Necropsy immediatley after the death showed no substance related morphological visible pathologic organ findings. The remaining animal showed no toxic symptoms . After that, 2 groups of 3 female rats were dosed with 50 mg/kg. No toxic symptoms were observed and no death occurred. No apparent changes were found in body weights of remaining rats. All survived animals showed

no substance related morphological visible pathologic organ findings.

The LD50 cut-off for VESTAMIN EP-HS 10 is 300 mg/kg. Ranking of the test substance VESTAMIN EP-HS 10 according to the Global Harmonised System resulted in Category 3: > 50 - 300 mg/kg

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

300 mg/kg bw

Quality of whole database:

The study is valid without restriction (Klimisch 1).

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:

1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with national standard methods with acceptable restrictions.

Qualifier:

equivalent or similar to guideline

Guideline:

other: 40CFR Part 158 Series 81-2, EPA Pesticide Assessment Guidelines. F 1984

Deviations:

no

Principles of method if other than guideline:

The test substance was dosed at a level of 1.0 g/kg. A group of animals (5 male 5 female) with healty intact skin was used. The substance was applied to approxinately 10% of the body surface.of each animal. The dressings were removed after 24 hours and observed over a period of 14 days for any sign of toxicity.

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

The New Zealand White rabbit, weighing 2.0 to 3.0 kg, was used for this study. The animals were obtained
from Buckshire Corp., Perkasie, PA 18944 (U.S.D.A. License #23-BL).
The animals were individually housed and maintained in accordance with standards set forth in the Guide for
the Care and Use of Laboratory Animals (NIH Publication No. 86-23). The rabbits were acclimated to the
laboratory for at least 5 days prior to dosing.

Temperature: 60°F - 75°F
Relative Humidity: 30-80%
Light: 12 hour light/dark cycle
Diet: Wayne 15% Rabbit Ration and tap water were provided ad libitum. Based on our current
knowledge, no contaminants are known to be in this diet or water which might be expected to
interfere with the objectives of the study.
Caging: Stainless steel elevated wire mesh flooring, 1 rabbit/cage.
The animals were individually identified by an ear tag and each cage was identified with a cage card.

Type of coverage:

occlusive

Vehicle:

other: Isopropanol

Details on dermal exposure:

The test article was dosed as supplied, at a dose level of 1.0 g/kg
A group of 10 rabbits (5 male & 5 female) with healthy intact skin was used. Approximately 24 hours before
testing, the fur was clipped from the backs of the test animals.
All rabbits were weighed and the correct amount of test article was applied to approximately 10% of the
body surface on each animal. The treated area was covered with a large porous gauze patch and wrapped
with an occlusive material and held in place with an elastic bandage to ensure that the animal did not
ingest the test article. The dressings were removed after 24 hours and any excess material removed, where
practical, using water or an appropriate solvent.

Duration of exposure:

24 hours

Doses:

1 g/kg

No. of animals per sex per dose:

5 male
5 female

Control animals:

no

Details on study design:

The animals were observed for a 14 day period, for signs of toxicity (systemic and topical) and for
mortalities. Animals were observed frequently during the first day of dosing, and twice per day (morning
and afternoon) on weekdays. On weekends and holidays, animals were observed once per day.
Individual weights were recorded on the day of dosing, weekly thereafter, and prior to sacrifice. The
animals were euthanized using T-61@ at the conclusion of the observation period. Gross necropsies were
performed on all animals.

Statistics:

no data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: Males: Necrotic skin and severe edema was noted after unwrapping at 24 hours. At 7 days 5/5 animals exhibited necrotic skin and severe edema. At 14 days, 3/5 animals exhibited necrotic skin and severe edema, 1/5 animals exhibited peeling necrotic skin and

Gross pathology:

No gross abnormalities were noted for 5/5 males necropsied at the conclusion of the 14 day observation period.
No gross abnormalities were noted for 5/5 females necropsied at the conclusion of the 14 day observation period.

Other findings:

none

Conclusions:

The acute dermal toxicity of Formaldehyde, polymer with benzenamine, hydrogenated appears to be greater than 700 mg/kg. At this dose level the test material was corrosive to skin but no mortalities occurred.

Executive summary:

Formaldehyde, polymer with benzenamine, hydrogenated when dosed at a 70% concentration in isopropanol and studied in male and female albino rabbits combined was corrosive to the skin and had an acute dermal LD50 >1000 mg/kg.

The LD50 in male and female rabbits, based on the substance (formaldehyde, polymer with benzenamine, hydrogenated) appears to be >700 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

700 mg/kg bw

Quality of whole database:

Test procedure in accordance with national standard methods with acceptable restrictions (Klimisch 2).

Additional information

Key study shows that the oral LD50 of formaldehyde, polymer with benzenamine, hydrogenated in rats is > 50 - 300 mg/kg (Evonik_Stockhausen, 2005).

The dermal LD50 in rabbits is >700 mg/kg (no deaths were observed, but necrotic skin and severe edema was noted in males and females)

(Reilly, 1988). Testing for dermal toxicity at higher doses is not warranted as the material is corrosive to the skin.

Justification for selection of acute toxicity – oral endpoint

The acute oral toxicity study by Eicler et al (Evonik_Stockhausen, 2005) is a fully acceptable key study (Klimisch1) with a LD50 cut off value of 300 mg/kg bw.

There are three other acute oral toxicity studies available with indications of toxicity near the cut off value of 300 mg/kg bw.

After taking account all available data and considering the most sensitive study amongst the valid ones, ranking the test substance according to GHS is resulted in Cat 3: > 50 - 300 mg/kg bw.

Justification for classification or non-classification

Based on the results of the acute oral toxicity studies and according to the Globally Harmonized Classification System (GHS) the test item is classified in the hazard category 3, required labelling with 'Danger' and 'Toxic if swallowed'. According to the EC Regulation 1272/2008 and subsequent regulations, the test item required labelling with 'Danger' and 'H301: Toxic if swallowed'.

As the test substance is corrosive to the skin, classification for dermal toxicity is not warranted based on the available data.