Reaction mass of 2,2'-(vinylenedi-p-phenylene)bis[5-methylbenzoxazole] and 2,2'-(vinylenedi-p- phenylene)bisbenzoxazole and 2-[4-[2-[4-(benzoxazol-2- yl)phenyl]vinyl]phenyl]-5-methylbenzoxazole

Endpoint summary

Description of key information

Oral LD50 (male and female) > 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:

February from 02 to 15, 1988

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:

adopted 24th February 1987

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

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: Hoechst AG, Kastengrund, SPF-Zucht.
- Age at study initiation: 7 weeks males and 6 weeks females.
- Weight at study initiation: males mean 180 g (173 - 189 g); females mean 167 g (161 - 170 g).
- Fasting period before study: the feed was suspended 16 hours before the treatment and was resumed 3-4 hours after the treatment.
- Housing: fully-air-conditioned rooms, in Makrolon cages (type 4) on limewood granules; groups of 5 animals.
- Diet: standard diet Altromin 1324, ad libitum.
- Water. tap water, ad libitum.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 50 ± 20 %
- Photoperiod: 12 hours daily.

Route of administration:

oral: gavage

Vehicle:

other: strength mash (potato starch in deionized water)

Details on oral exposure:

VEHICLE
- Preparation: test item was suspended in a 2 % strength mash (potato starch in deionized water) using a mortar and pestle and homogeneously distributed using a magnetic stirrer.
- Concentration: 20 % (w/w)
- Application volume: 10 ml/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weight of the animals was determined weekly.
- Necropsy of survivors performed: yes; at the end of the observation period, the test animals were killed by carbon dioxide, dissected and examined for macroscopically visible changes.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No death occurred.

Clinical signs:

No symptoms occurred during the entire observation period.

Body weight:

No impairment of body weight development was recorded.

Gross pathology:

The animals at the end of the post-observation period were free of macroscopically visible changes.

Interpretation of results:

other: not classified, according to the CLP Regulation ((EC 1272/2008)

Conclusions:

LD50 (male and female) > 2000 mg/kg bw

Executive summary:

The acute oral toxicity potential of test item was investigated according to the procedures outlined into the OECD guideline 401 and according to the EU Method B.1. 5 males and 5 females rats were treated at a dosage level of 2000 mg/kg bw. The test item was suspended in a 2 % strength mash (potato starch in deionized water) using a mortar and pestle and homogeneously distributed using a magnetic stirrer; the substance was administered as a single dose by gavage. After administration of the compound, the animals were observed for 14 days; at the end of the observation period, surviving animals were killed and an autopsy performed.

No death occurred and no symptoms were observed during the entire observation period. No impairment of body weight development was recorded. The animals at the end of the post-observation period were free of macroscopically visible changes.

Conclusion

LD50 (male and female) > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

ACUTE TOXICITY - ORAL ROUTE

The acute oral toxicity petential of the test item was investigated according to the procedures outlined into the OECD guideline 401 and according to the EU Method B.1. 5 males and 5 females rats were treated at a dosage level of 2000 mg/kg bw. No death occurred and no symptoms were observed during the entire observation period. No impairment of body weight development was recorded. The animals at the end of the post-observation period were free of macroscopically visible changes.

A second experiment is also available, in which females rats were treated at a dosage level of 15000 mg/kg bw. 40 to 60 minutes after application, the treated animals showed squatting position and after two to three hours skin reddening. 24 hours post-application, poisoning symptoms resulted to be recovered in all animals. The excretion of the substance occurred via the excrement (yellow discolored after 24 hours). The body weight development during the observation period was normal. The gross assessment did not reveal any abnormality.

ACUTE TOXICTY - INHALATION ROUTE

No acute toxicity studies by inhalation route are available on Fluorescent Brightener 219. However, because of the physical state of the substance inhalation is not an appropriate route of exposure. The vapour pressure of the substance is estimated to be negligible; the particle size distribution showed that the 97.1 % of particles have a diameter higher than 100 µm and that the 98.4 % of particles has a diameter higher than 45 µm. Thus, Fluorescent Brightener 219 is characterized by particles not-respirable. This consideration, along with the consideration that the substance is manufactured and handled with suitable risk management measures and with the suitable personal protective equipments, lets to consider the possible absorption of the substance by inhalation route as negligible.

ACUTE TOXICITY - DERMAL ROUTE

The inhalation and the skin contact of Fluorescent Brightener 219 are unlikely.

According to the REACH Regulation, Annex VIII, Column 1 Standard information required, testing by the dermal route does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation).

Furthermore, in the Commission Regulation (EU) 2016/863, amending Annexes VII and VIII to REACH Regulation (EC 1907/2006), it is explained that recent scientific analysis of available data from in vivo acute toxicity studies have shown that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. Therefore, testing those substances via the dermal route does not provide essential information for their safety assessment. The amendment is the consequence of studies and scientific debates. In particular, the 15th Meeting of Competent Authorities for REACH and CLP (CARACAL, 2014) concluded that an adaptation of point 8.5.3 of Annex VIII to REACH is justified in order to not require information on acute dermal toxicity for substances that have shown no toxicity in acute oral toxicity test up to the limit dose of 2000 mg/kg bw.

In the oral acute toxicity tests no signs of systemic toxicity were recorded. The skin sensitisation potential was investigated in Local Lymph Node Assay (LLNA) and no test item-related systemic clinical signs were observed. No reason of concern is raised on the basis of the skin/eye irritation investigations.

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), 3.1 Acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

The oral LD50 value was established to be greater than 2000 mg/kg body weight, therefore the test substance is out of any classification limit for acute oral toxicity (oral acute toxicity category 4: 300 < ATE ≤ 2000 mg/kg bw).

Dermal and inhalation exposure is unlikely, thus no acute toxicity value is available and no further investigation is required.

In conclusion, the test substance does not meet the criteria to be classified for oral acute toxicity, according to the CLP Regulation (EC 1272/2008).