Formaldehyde, reaction products with diethanolamine and 6(or 7)-methyl-1H-benzotriazole

Endpoint summary

Description of key information

- LD50 acute oral toxicity (male and female; rat) = 1472 mg/kg bw (Ciba-Geigy Ltd, 1981)

- LD50 acute dermal toxicity (male and female; rat) > 2000 mg/kg (Read across subtance) (Bioassay, 2012)

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:

October 5, 1981 - October 19, 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(limited documentation (test substance, gross pathology), acclimation period 4 days)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 175 g (males) and 167 g (females)
- Fasting period before study: overnight
- Housing: groups of 5 in Macrolon cages (type 3)
- Diet: NAFAG No. 890, NAFAG, Gossau SG; ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

containing 0.5% CMC

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

500, 1000 and 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: 1, 2, 3, 5 and 24 h after treatment and then daily until day 14
- Frequency of weighing: day 1, 7 and 14
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs, body weight

Statistics:

The LD50, including the 95% confidence limits were calculated by the logit model.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 472 mg/kg bw

Based on:

test mat.

95% CL:

> 1 104 - < 2 298

Mortality:

- 500 mg/kg bw: 0/10
- 1000 mg/kg bw: 1/10
- 2000 mg/kg bw: 8/10

Clinical signs:

other: Sedation, dyspnoea, ruffled fur, ventral/lateral/curved body position

Gross pathology:

no data

Table 1: Table for acute oral toxicity

 

Dose [mg/kg bw]	Mortality*	Time of death	Mortality (%)
Males
500	0/5	---	0
1000	1/5	Day 1	20
2000	3/5	Day 1	60
Females
500	0/5	---	0
1000	0/5	---	0
2000	5/5	Day 1	100
LD50 = 1472 mg/kg bw

                                                                                            

* first number = number of dead animals                                   

 second number = number of animals used                             

 

Table 2: Clinical symptoms

Signs/Symptoms	Dose (mg/kg bw)
	500	1000	2000
Sedation	---	1 h – day 3	1 h – 5 h
Dyspnoea	1 h – day 9	1 h – day 9	1 h – day 9
Ruffled fur	1 h – day 8	1 h – day 8	1 h – day 8
Ventral body position	1 h	1 h	1 h – 5 h
Curved body position	1 h – day 7	1 h – day 7	1 h – 7 h
Lateral body position	---	---	1 h – 3 h

 

Table 3: Mean body weights (g)

Dose [mg/kg bw]	Day 1	Day 7	Day 14
Males
500	173	233	277
1000	175	229	273
2000	179	228	266
Females
500	164	194	214
1000	172	201	221
2000	164	---	---

 

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 of the test article in rats of both sexes observed over a period of 14 days is 1472 (1104-2298) mg/kg. The test material is therefore slightly toxic to the rat by this route of administration.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

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:

November 05, 2012 - December 06, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

other: Japan MAFF 8147

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515/519, 69120 Heidelberg

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
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: males animals approx. 230 g, female animals approx. 212 g
- Housing: single housing in Makrolon cage, type III; bedding: H 15005-29; Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany); enrichment: NGM E-022; ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: about 40 cm²
- % coverage: 10
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2.11 mL/kg bw

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: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Necropsy of survivors performed: yes
- Other examinations performed: Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times until the last day of observation. The evaluation of skin reactions was performed according to Draize, J.H. (1959).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination. Local effects: In all male animals well-defined erythema (grade 2) was noted on study day 1 and persisted in one animal until study day 3. In the other four animals moderate erythema

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, the acute dermal median lethal dose (LD50) was determined to be greater than 2000 mg/kg bw,

Executive summary:

In an acute dermal toxicity study (Limit Test) following OECD guideline 402 and in compliance with GLP, young adult Wistar rats (5 males and 5 females) were dermally treated with a single dose of 2000 mg/kg bw of the undiluted test item to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred and no signs of systemic toxicity were observed. The following test item-related local effects were recorded during the course of the study: very slight to moderate erythema (grade 1 to 3), very slight to slight edema (grade 1 to 2), incrustations and scaling. The mean body weight of the animals increased within the normal range throughout the study period. No macroscopic pathologic abnormalities were noted in the animals examined at

the end of the study. Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute Oral Toxicity  

In a standard acute oral toxicity study performed similarly to OECD TG 401, groups (5 rats/sex/dose) of young RAIf rats were administered the test substance (no data on purity) after an overnight fasting period. The test substance was administered at doses of 500, 1000 and 2000 mg/kg bw in water containing 0.5% CMC. Animals were subsequently observed for 14 days and clinical signs of toxicity, body weight changes and cases of mortality were noted. In the low dose group, no animal died. In the mid and high dose group 1/10 and 8/10 animals died, respectively. Hence the LD50 is 1472 mg/kg bw. Dyspnoea, ruffled fur, ventral and curved body position were seen in all dose groups, sedation in the mid and high dose group and lateral body position only in the high dose group. All surviving animals recovered latest on day 9. No compound related findings were observed during necropsy and changes in body weight were within the normal range (Ciba Geigy Ltd. 1981).

Acute Dermal Toxicity

Acute dermal toxicity of the test article is assessed by read across approach to a structurally related compound (see CSR for read across justification).

In an acute dermal toxicity study (Limit Test) performed according to OECD guideline 402 and under GLP, young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test substance to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours (Bioassay, 2012). The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred and no signs of systemic toxicity were observed. The following test item-related local effects were recorded during the course of the study: very slight to moderate erythema (grade 1 to 3), very slight to slight edema (grade 1 to 2), incrustations and scaling. The mean body weight of the animals increased within the normal range throughout the study period. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. Based on the results of this study, the acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg bw.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for the purpose of classification. Based on the criteria laid down in Regulation (EC) No. 1272/2008, classification "category 4" for acute oral toxicity is warranted.