Registration Dossier

Diss Factsheets

Administrative data

Description of key information

oral
Acute oral toxicity (BASF AG 85/16): LD50 (males + females) > 2000 mg/kg bw and < 5000 mg/kg bw
Acute oral toxicity (Hoechst AG 84.0195): LD50 (males + females) = 3300 mg/kg bw

inhalation
Acute inhalation toxicity, aerosol (Hoechst 84.0378): LC50 (males + females) = 2.44 mg/L air

Acute inhalation toxicity, dust (Hoechst 84.0693): LC50 (males + females) > 1.3 mg/L air

dermal
Acute dermal toxicity (BASF AG 85/248): LD50 (males + females) > 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:
1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1981)
Qualifier:
according to guideline
Guideline:
other: EEC Directive 79-831, Annex V, Part B: Methods For The Determination Of Toxicity, 4.1.1 Acute Toxicity Orally
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Code HF 0001

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the dark, at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Glyoxal as 40% aqueous solution is stable for 6 months

OTHER
- Impurities (identity and concentrations): acetic acid, formic acid, glycolic acid, glyoxylic acid, nitric acid, formaldehyde, acetaldehyde, glycol aldehyde, ethylene glycol
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF-Zucht
- Weight at study initiation: males, 190.3 g (182 - 203 g); females, 177.9 g (165 - 193 g)
- Fasting period before study: 16 hours prior and 2 hours after treatment
- Housing: five animals per cage, in Makrolon cages
- Diet (e.g. ad libitum): rat feed (Rattendiaet Altromin 1324), ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): housing in fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 h/ 12 h
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- The concentration of test substance in vehicle was 25 % as w/v, for each dose level
- The application volume was 8, 12.6 and 20 mL/kg bw for the 2000, the 3150 and the 5000 mg/kg bw dose level, respectively
Doses:
2000, 3150 and 5000 mg/kg bw of test substance containing 40% a.i., i.e. 800, 1260 and 2000 mg/kg bw of active ingredient
No. of animals per sex per dose:
10 animals/sex/dose
Control animals:
no
Details on study design:
- The treatment was followed by a 14-day post -exposure period of observation;
- The animals were observed for mortality and clinical symptoms of toxicity several times, as recommended by the OECD guideline;
- Body weight was recorded once a week;
- Animals that died during the 14-day observation period were subjected to necropsy and were examined for gross pathology;
- At the end of the observation period, the surviving animals were sacrificed for the purpose of necropsy.
Statistics:
The determination of the LD50 was based on the Probit Analysis
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 300 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
3 660 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
2 960 mg/kg bw
Mortality:
- In the 2000 mg/kg bw group:  0/5 males 1/5 females (i.e. 10% mortality)
- In the 3150 mg/kg bw group:  2/5 males 2/5 females (i.e. 40% mortality)
- In the 5000 mg/kg bw group:  4/5 males 5/5 females (i.e. 90% mortality)
- All cases of death occurred between 70 minutes and 24 hours following dosing.
Clinical signs:
other: - Clinical symptoms indicative of toxicity were seen in all groups and both sexes. - Following treatment, the animals showed decreased spontaneous activity, decreased respiration rate, increased water consumption, uncoordinated gait, squatting position,
Gross pathology:
- Necropsy of animals that died: partly firm small and large intestines filled with a colorless liquid, some cases of reddening of the stomach mucosa, spotted liver and dark discoloration of the adrenals, some cases of increased blood content in the lung, and some cases of grey-pink discoloration of the lung were reported.
- Necropsy of animals that survived and were sacrificed at the end of the observation period: no abnormalities were reported.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 300 mg/kg bw
Quality of whole database:
GLP study according OECD TG 401

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(1981)
Qualifier:
according to guideline
Guideline:
other: EEC Directive 79-831, Annex V, Part 8: Methods For The Determination Of Toxicity, 4.1.2 Acute Toxicity Inhalation
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Code HF 0001
- Purity test date: 21. 12. 1983

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: storage at 22 °C in the dark recommended
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF-Zucht
- Age at test initiation: 8 to 10 weeks
- Weight at study initiation: males, 186 g (175 – 210 g); females, 189.5 g (171 – 207 g)
- Fasting period before study: 16 hours prior and 2 hours after treatment
- Housing: five animals per cage, in Makrolon cages type 4
- Diet (e.g. ad libitum): rat feed (Rattendiaet Altromin 1324), ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 20
- Air changes (per hr): housing in fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 h/ 12 h
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The test substance was conducted at a constant rate through a permanent infusion apparatus into a special injector, where an air stream was entered by a compressor at 4 bar. The flow rate of the air stream was maintained constant at 800 L/hour (rotameter). A primary aerosol was so generated in a vessel and was conducted through an ascending tube into the exposure chamber; due to the ascending tube, only small aerosol particles, defined as secondary aerosol, reached the chamber from the top. The aerosol/air mixture was evacuated at the bottom of the chamber through a vacuum system with cotton filter and a 10% sodium hydroxide solution, at a rate of 1100 l/hour.

PARTICLE SIZE DISTRIBUTION
The test concentrations of aerosol in the exposure chamber were determined gravimetrically.
The size distribution of the test substance particles was determined by means of the particle counting system, model 225 (Kratel GmbH, Stuttgart, Germany). The mass median aerodynamic diameter (MMAD) was measured for the following size classes:
0.3 – 0.49 µm, 0.5 – 1.49 µm, 1.5 – 2.01 µm, 2.02 – 2.99 µm, 3.0 – 3.99 µm, 4.0 – 4.99 µm, 5.0 – 5.99 µm, and > 6.0 µm.

MONITORING OF CHAMBER PARAMETERS
During exposure, the CO, CO2, and O2 contents as well as the relative humidity and the temperature in the exposure chamber were measured.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
determination of the test substance was based on the use of an UV-detector (405 nm) after reaction with 2-hydrazono-2,3-dihydro-3-methylbenzthiazole hydrochloride in aqueous solution.
Duration of exposure:
4 h
Concentrations:
- The respective test concentrations were 2.20, 2.60 and 2.70 mg of unchanged test substance/l air (determined analytically).
- The corresponding application volumes were 45, 60 and 90 mL/hour, respectively.
No. of animals per sex per dose:
Five animals per sex and group were used
Control animals:
no
Details on study design:
- During exposure the animals were observed for clinical symptoms indicative of toxicity and for mortality;
- The treatment was followed by a 14-day post-exposure observation period; during this period the animals were regularly observed for clinical symptoms and mortality, and their body weights were recorded on day 2, 3, 4, 7 and 14. Dead animals were subjected to necropsy as soon as possible; the surviving animals were sacrificed at the end of the observation period for the purpose of necropsy.
Statistics:
The LC50 was determined by means of Probit Analysis.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
2.44 mg/L air (analytical)
95% CL:
2.23 - 2.59
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
2.47 mg/L air (analytical)
95% CL:
2.13 - 2.75
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
2.41 mg/L air (analytical)
95% CL:
2.04 - 2.67
Exp. duration:
4 h
Mortality:
-Mortality was 20%, 50% and 100% in each of the 2.20, 2.60 and 2.70 mg/L  group, respectively. Most cases of death occurred within the first day following treatment.
- In the 2.20 mg/L group, 2 animals died; 1 male was found dead after 18.5 hours following treatment, whereas 1 female was found dead on day 2.
- In the 2.60 mg/L group, 5 animals died; there from, 2 males and 2 females were found dead on day 1 post treatment whereas 1 female died on day 9.
- In the 2.70 mg/L group, all animals except for one female died within 1 day following treatment; the last female died on day 3 post treatment.
Clinical signs:
other: - Symptoms of toxicity were seen in all groups and comprised irregular breathing, reddish nasal discharge, intermittent respiration, gasping, noisy breathing, narrowed eyelids, sneezing, retracted flanks, piloerection, prone position, and drowsiness; - Th
Body weight:
For both sexes, a temporary loss in body weight was observed after 2 days following treatment; however, this effect was reversible within 7 days. For details, see table below.
Gross pathology:
Dead animals: both dead animals of the 2.20 mg/L group as well as 2 dead males and 2 dead females of the 2.70 mg/L group were autolytic at necropsy. Necropsy of the remaining animals that died revealed dark red lungs with foamy content.
Sacrificed animals: necropsy of the animals that were sacrificed at the end the observation period revealed no abnormalities.
Other findings:
- Particle size analysis demonstrated that for each test concentration, the respirable particle fraction < 3.0 µm was > 80% (i.e. respectively ca. 84, 81 and 85%).
- For details on monitored parameters and particle size analysis, see tables below.

Body weight data:

2.20 mg/L  group

Males

Females

Initial  body weight range

176-188 g (N=5)

171-182 g (N=5)

Body weight range, day 2

147-160 g (N=4)

149-163 g (N=5)

Body weight range, day 3

142-159 g (N=4)

157-165 g (N=4)

Body weight range, day 4

153-162 g (N=4)

158-164 g (N=4)

Body weight range, day 7

180-193 g (N=4)

173-183 g (N=4)

Body weight range, day 14

230-250 g (N=4)

195-205 g (N=4)

2.60 mg/L  group

Males

Females

Initial  body weight range

177-192 g (N=5)

178-196 g (N=5)

Body weight range, day 2

167-174 g (N=3)

156-178 g (N=3)

Body weight range, day 3

170-173 g (N=3)

149-163 g (N=3)

Body weight range, day 4

179-182 g (N=3)

147-160 g (N=3)

Body weight range, day 7

214-219 g (N=3)

134-154 g (N=3)

Body weight range, day 14

251-262 g (N=3)

175, 178 g (N=2)

2.70 mg/L  group

Males

Females

Initial  body weight range

175-210 g (N=5)

191-207 g (N=5)

Body weight ranges

Not applicable because of mortality

Not applicable because of mortality

Exposure chamber, monitored parameters:

Parameters

Monitored values in the exposure chamber for each test group

2.20 mg/L

2.60 mg/L

2.70 mg/L

CO (ppm)

2

0

2 – 4

CO2 (ppm)

2900 – 3500

2000 – 3100

2100 – 3100

O2 (%vol.)

19.6 – 19.7

20.1

20.4 – 20.5

Temperature (°C)

23.6 – 24.2

23.0 – 24.2

23.3 – 23.9

Rel. humidity (%)

81.6  – 94.0

100

98.5 - 100

Particle size analysis, results:

Particle size interval (µm)

Particle fraction (%)

2.20 mg/L

2.60 mg/L

2.70 mg/L

0.3 – 0.49

25.1

31.1

25.3

0.5 – 1.49

33.9

29.3

32.1

1.5 – 2.01

14.8

11.8

16.1

2.02 – 2.99

9.8

9.1

11.7

3.0 – 3.99

4.8

8.9

5.9

4.0 – 4.99

4.0

4.5

5.2

5.0 – 5.99

2.2

2.8

2.6

> 6.0

5.5

6.5

5.0

Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
2 440 mg/m³ air
Quality of whole database:
GLP study according 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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The test method was comparable to the limit test as described by OECD guideline 402 (1987) without GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
((limit test, 1987)
GLP compliance:
no
Remarks:
the study was carried out in a GLP certified laboratory. However, the study was not monitored by the QAU; therefore, the study was not fully compliant to GLP requirements.
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Tank B 401

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: Glyoxal as 40% aqueous solution is stable for 6 months

OTHER
- Impurities (identity and concentrations): ethylene glycol, glycol aldehyde, formaldehyde, formic acid, glycolic acid, glyoxylic acid)
- Composition of test material, percentage of components: Glyoxal 40%, ethylene glycol 0.6%, glycol aldehyde 0.15%, formaldehyde 0.015%, formic acid, glycolic acid, glyoxylic acid, 0.1%)

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, D-7950 Biberach, Germany
- Weight at study initiation:
mean body weight of the males: 269 g
mean body weight of the females: 227 g
- Fasting period before study: no
- Housing: single housing in steel wire mesh cages, type OK-III (Becker & co. Castrop-Rauxel, Germany)
- Diet (e.g. ad libitum): Kliba-Labordiaet, FA. Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): housing in fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 h/ 12 h
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
Each animal received a single application of unchanged test substance on the clipped skin within the dorsal to dorsolateral region of the trunk; clipping of the fur had been done at least 15 hours prior to treatment. The application volume was 1.57 mL/kg bw and the tested dose level was 2000 mg/kg bw. The application site was covered with a semiocclusive dressing for 24 hours; thereafter, dressing was removed and the application site was rinsed with warm water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
10 animals/sex/group were used
Control animals:
no
Details on study design:
- The treatment was followed by a 14-day post -exposure period of observation;
- The animals were observed for mortality twice each workday and once daily at weekends or public holidays;
- They were examined for clinical symptoms of toxicity several times during the application day and at least once daily thereafter;
- Skin findings were scored 30 to 60 minutes following removal of the dressing, and at least once weekly during the observation period;
- The rats were weighed prior treatment and thereafter, on day 2, 7 and 13 post-treatment;
- At the end of the observation period, the surviving animals were sacrificed for the purpose of necropsy;
- Animals that died during the observations period also were subjected to necropsy.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Neither mortality nor symptoms of toxicity were seen at the tested dose level of 2000 mg/kg bw.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 800 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: Neither mortality nor symptoms of toxicity were seen at the tested dose level of 2000 mg/kg bw of test material Glyoxal 40%, i.e., 800 mg/kg bw of the active ingredient.
Mortality:
No mortalities were observed.
Clinical signs:
other: No clinical symptoms of toxicity were observed.
Gross pathology:
All animals survived and were sacrificed at the end of the observation period; necropsy revealed no abnormalities.
Other findings:
Skin examination revealed erythema in both males and females on day 1 following treatment.

Body weight data:

Time point of body weight recording

Males (mean body weight, N = 5)

Females (mean body weight, N = 5)

Initial

269 g

227 g

Day 2

253 g

218 g

Day 7

278 g

230 g

Day 13

347 g

240 g

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
study according OECD TG 402

Additional information

Acute oral

In a study performed according OECD TG 401 Wistar rats of both sexes were dosed orally with 2000, 3150 and 5000 mg/kg bw of Glyoxal 40%. The LD50 was 3660 mg/kg bw for the males, 2960 mg/kg bw for the females, and 3300 mg/kg bw for both sexes, respectively (Hoechst AG 84.0195). In a further study according OECD TG 401, the acute oral toxicity of Glyoxal (40% aqueous solution) was determined using Wistar rats of both sexes. The LD50 was greater than 2000 and lower than 5000 mg/kg bw (BASF AG 85/16). An "all-or-none" mortality response was observed, since almost all animals of the 5000 mg/kg bw group died during the first day following treatment, whereas no mortality was seen in the group treated with 2000 mg/kg bw of test substance.

In a supporting study similar to OECD TG 401, young adult rabbits were treated by gavage with preparations of Glyoxal 40% aqueous solution. The study was conducted to assess treatment-related changes in serum urea level, liver function, urine and body weight gain during an observation period of 8 weeks. The liver function was not altered and analysis of urine revealed no abnormalities. Changes in body weight and serum urea level observed during the first days following treatment returned to normal within 20 days (BASF SE XIII/258).

In a further study the test item was administered by gavage to female Wistar rats and observed for a period of 14 days. The LD50 was determined to be > 762 mg/kg bw (Society Francaise Hoechst SE 84/0280). In another study the acute oral toxicity of Glyoxal (40%) was investigated after single application in male rats and the LD50 was 1910 mg/kg bw (BASF SE 851).

Acute inhalation

Referring to the inhalative toxicity, Glyoxal 40% as aerosol was shown to be harmful by inhalation. An LC50 value of 2.44 mg/L air was reported for Wistar rats of both sexes following nose-only exposure for 4 hours to analytical concentrations of Glyoxal of 2.2, 2.6 and 2.7 mg/L air (Hoechst 84.0378; 1984). Mortalities (20, 50, and 100%, respectively) were seen at all three concentrations tested. A further acute inhalation toxicity study was conducted with Glyoxal 80 (white powder, purity 80%); the rats were exposed to the technically highest possible Glyoxal (dust) concentration of 1.3 mg/L air (Hoechst 84.0693; 1984). No mortalities were observed. Thus, the LC50 in the present case was > 1.3 mg/L air for both sexes.

In Inhalation Risk Tests Sprague-Dawley rats were whole-body exposed to an atmosphere saturated with volatile components of the test item for 7 hours. The test concentration was estimated to be 11.56 mg/L air. None of the animals died. An LC50 > 11.56 mg/L air was deduced (BASF SE 77/99). In further Inhalation Hazard Tests conducted as described in Annex 5 of the OECD TG 403 dated 1981, Wistar rats were nose only exposed to an atmosphere saturated with volatile components of Glyoxal 40T or Glyoxal 40N at 20 °C and for 7 hours. None of the animals died during exposure. Irregular respiration frequency was noticed (Hoechst 84.0443; Hoechst 84.0450). When 12 rats (sex not specified) were whole body exposed to an atmosphere saturated with volatile components of Glyoxal (30-40%) at 20°C and for 8 hours, none of the animals died (BASF SE XIII/258; BASF SE XII/257).

Acute dermal

The acute toxic potential for the dermal route was examined after a single semi-occlusive application of Glyoxal 40% aqueous solution at a dose level of 2000 mg/kg bw to the skin of Wistar rats of both sexes. Neither mortality nor clinical symptoms of toxicity were observed (BASF AG 85/248; 1985). Thus, the LD50 for both, males and females, was > 2000 mg/kg bw.

Justification for classification or non-classification

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

The substance is already listed in Annex VI of Regulation (EC) No 1272/2008 and classified with Cat. 4* (H332:" Harmful if inhaled";*meaning minimum classification for this category).

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No 1272/2008.

Due to the inhalative toxicity of the aerosol observed for this test item (rat 4 h; LC50=2.44 mg/L), the substance is considered to be classified for acute inhalative toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776. No classification and labeling is warranted for acute dermal and oral toxicity.