glyoxal … %; ethandial … %

Endpoint summary

Description of key information

Glyoxal 40% tested in a GPMT study, in further Bueher studies and in a LLNA was sensitizing in all studies.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

(1981)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Test was performed before the LLNA guideline was available.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Tank 409

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: cooling
- Stability under test conditions: stability has been demonstrated by analysis when stored at ca. 8 °C

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Lippische Versuchstierzucht, Hagemann GmbH & Co. KG, Extertal, Germany
- Weight range at study initiation: 250-309 g
- Housing: 5 animals per cage, Makrolon cage type IV
- Diet: 341.4 mm (Kaninchen-Meerschweinchen-Haltungsdiät), FA. Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland, ad libitum
- Water: Tap water ad libitum, supplemented twice a week with about 2 g of ascorbic acid per 10 litres of water
- Acclimation period: at least 7 days prior test initiation

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

REMARK:
- The feed used in the study was assayed for contaminants. In view of the aim and duration of the study the contaminants occuring in commercial feed did not influence the results.
- The drinking water is regularly assayed for contaminants by the municipal authorities of Frankenthal and the Technical Services of BASF SE. In view of the aim and duration of the study there were no special requirements exceeding the specifications of the drinking water.

Route:

intradermal and epicutaneous

Vehicle:

water

Concentration / amount:

- The concentrations used for testing were selected on the basis of the results of a pretest;
- For the first induction, the test substance was used as 20% solution in either distilled water or Freund´s adjuvant/water (1:1);
- For the second induction, the test substance was used as such, i.e. unchanged;
- For both challenges, the test substance was used as 10% solution in distilled water;
- All test solutions were prepared immediately prior treatment, using an Ultraturrax or a magnetic stirrer for mixing.

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

- The concentrations used for testing were selected on the basis of the results of a pretest;
- For the first induction, the test substance was used as 20% solution in either distilled water or Freund´s adjuvant/water (1:1);
- For the second induction, the test substance was used as such, i.e. unchanged;
- For both challenges, the test substance was used as 10% solution in distilled water;
- All test solutions were prepared immediately prior treatment, using an Ultraturrax or a magnetic stirrer for mixing.

No. of animals per dose:

10 animals per control group (2 groups)
20 animals per test group

Details on study design:

- The test method was based on Magnusson and Kligman (J. Invest. Dermatol. 52, 268-276, 1969)
- A test group of 20 and two control groups of respectively 10 Pirbright White, Dunkin, Hartley guinea pigs were used for the adjuvant test procedure; the test concentrations were selected upon the results of a preliminary test.
- The first induction was intradermal, and the test substance was used as 20% solution in distilled water, resp. in Freund´s adjuvant/water (1:1).- The second induction was percutaneous occlusive and the test substance was applied unchanged.
- The two challenges were percutaneous occlusive, and the test substance was used as 10% solution in distilled water; skin readings were performed after 24, 38 and 72 hours following each challenge.
- As recommended by Annex VI/II D of the Council Directive of July 29, 1983 for the 5th Amendment of the Directive 67/548 EEC (= 83/467 EEC), the results were considered to be positive when at least 30% of the experimental animals exhibit skin reactions; furthermore, only the findings obtained 48 hours after application were taken into account for the determination of the sensitization rate.
- Negative controls: the control animals were used to rule out a substance-induced primary skin irritation.

Positive control substance(s):

yes

Remarks:

dinitrochlorobenzene (DNCB) was tested twice a year as positive control substance on the selected guinea pig strain in the testing laboratory.

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

10% TS in aqua dest.

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

Control group 1: after both challenges, no positive skin reaction was seen. Control group 2: This control group only was considered for rechallenge; no positive skin reaction was seen.

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10% TS in aqua dest.

No. with + reactions:

7

Total no. in group:

19

Clinical observations:

One animal in the test group died 7 days after intradermal induction. After the first challenge and at reading time point 48 h, 7/19 animals showed positive skin reactions, consisting mostly of distinct erythema.

Key result

Reading:

rechallenge

Hours after challenge:

48

Group:

test chemical

Dose level:

10% TS in aqua dest.

No. with + reactions:

11

Total no. in group:

19

Clinical observations:

After the second challenge, 11/19 animals were scored positive (slight to distinct erythema).

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Glyoxal (40% aqueous solution) was tested for skin sensitization in the guinea pig maximisation test (GPMT) according to the OECD TG 406 (BASF AG 30H342/86; 1987). In the glyoxal (40%) treated test group, 7/19 animals (i.e. 37%) showed positive skin reactions mostly consisting of distinct erythema after the first challenge, at reading time point 48 h; after a second challenge, 11/19 animals were still scored positive (i.e. 58%) as they displayed slight to distinct erythema. For both challenges, the percentage of animals exhibiting positive skin reaction was > 30%

The results of a Magnusson and Kligman test (modified) published by Foussereau et al. (1992), those of a further GPMT (Pharmakon Research PH 423-AC-001-84), those of a Buehler Test (Bio/Dynamics Inc. 5529/85; 1988) and those of a LLNA test (Basketter DA 1999) were further considered for support.

Glyoxal 40% tested in the key GPMT study was found to be sensitizing in all studies.

Respiratory sensitisation

Endpoint conclusion

Additional information:

Glyoxal, generated from simulated indoor air chemistry was identified as skin sensitizer using QSAR modeling, LLNA and, phenotypic analysis. Dermal exposure of mice to glyoxal, glycolaldehyde, and diacetyl did not result in biologically significant elevations in the IgE+B220+ cell populations or IgE levels according to the criteria described by Manetz and Meade (1999). Based on the predictions of these screening tools, glyoxal, glycolaldehyde, and diacetyl would be classified as likely T-cell-mediated sensitizers.Further analyses are necessary to identify the potential for the chemicals tested positive in the LLNA to be respiratory sensitizers (Anderson et al, 2007).

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 skin sensitizing Cat. 1 (H317:”May cause an allergic skin reaction”).

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No 1272/2008. Based on these information the test item is considered to be classified for skin sensitisation Cat. 1 under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.