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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study is in compliance with OECD 401 and was carried out under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Hydrogen peroxide
EC Number:
231-765-0
EC Name:
Hydrogen peroxide
Cas Number:
7722-84-1
IUPAC Name:
hydrogen peroxide
Details on test material:
Hydrogen peroxide, 70% w/w

Test animals

Species:
rat
Strain:
other: Crl:CD BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Raleigh, North Carolina
- Age at study initiation: male rats were 56-62 days old, female rats were 63-66 days old
- Weight at study initiation: males weighed between 222 and 242 g, females weighed between 191 and 194 g
- Fasting period before study: approximately 18 hours
- Housing: Singly in suspended, stainless steel, wire-mash cages
- Diet (e.g. ad libitum): Purina certified Rodent Chow, #5002 ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 1 °C
- Humidity (%): 50 +/- 10 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
see Table 1
Doses:
nominal doses were 500, 1000 and 1500 mg/kg body weight in males and 500, 750 and 1000 mg/kg body weight in females
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Animals were observed for 14 days after the administration of the single dose of hydrogen peroxide. All rats on study were examined grossly at necropsy either when found dead or sacrificed by design after cessation of the observation period. All animals were checked daily for mortality and clinical signs.
Statistics:
Method of determination of LD50: Finney, D.J. (Probit analysis, 3rd. Ed., Cambridge University Press, 1971)

Results and discussion

Preliminary study:
none
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 026 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
693.7 mg/kg bw
95% CL:
427 - 960
Mortality:
2 males in the 1000 mg/kg dose group and 5 males in the 1500 mg/kg dose group were found dead before the end of the observation period.
1 female in the 500 mg/kg dose group, 2 females in the 750 mg/kg dose group and 5 females in the 1000 mg/kg dose group were found dead before the end of the observation period.
Clinical signs:
Clinical signs of toxicity were observed in all dose groups, and included lethargy, immobility, irregular respiration, and hunced posture. Other clinical signs were low posture, low carriage, red ocular discharge and ruffled fur.
Body weight:
Body weight gain was depressed in a dose-dependent manner.
Gross pathology:
Gross findings included discoloration of the tongue, fluid in the esophagus, thickened and discolorated stomach with observed fluid, ulcer/erosion of the stomach, discoloration of the duodenum and fluid formation in the tissue, fluid in the peritoneal cavity and adhesion of stomach, liver and spleen.
Other findings:
Microscopic findings: degenerative (ulcer) and regenerative (hyperplasia) alterations in the mucosa and/or submucosa of the plyoric antrum of the stomach were present in males at 500 (2/5), 1000 (2/5) and 1500 (1/5) mg/kg levels and in females at the 500 (3/5) and 750 (3/5) mg/kg levels. Ulcerswere focal areas of necrosis of the epithelium, lamina propria and muscularis mucosa. Inflammation was not diagnosed accompanying an ulcer, as it was considered a component of the ulcer diagnosis. Pyloric mucosal hyperplasia was characterised by increased gland height and goblet cells full of mucus and was most often seen near ulcers. In other instances, mucosal hyperplasia was accompanied by inflammation and these changes togehter were considered indicative of irritation that had not progressed to ulceration. Small to large irregularly round to oval clear spaces were detected in the mucosa, submucosa and tunica muscularis of the stomachs of all rats found dead on test day 1. The spaces were interpreted to be accumulations of gas, probably oxygen.
The stomach lesions noted in rats sacrificed by design were considered morphologically reparable upon cessation of treatment with hydrgen peroxide, although scar tissue might focally replace the muscularis mucosa at sites of ulceration.

Any other information on results incl. tables

Table 1: Results of the acute oral toxicity test in male and female rats

Dose [mg/kg bw]

Number of dead

Dose volume (mL/kg)

male

female

male

female

500

0/5

1/5

0.39

0.39

750

-

2/5

-

0.58

1000

2/5

5/5-

0.78

0.78

1500

5/5

1.16

-

LD50 value

1026 mg/kg bw

694 mg/kg bw

Combined LD50: 805 mg/kg bw

 

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
70% hydrogen peroxide is classified as harmful if swallowed (R22; Xn) according to Directive 2001/59/EC (adaptation of 67/548/EEC) and is classified with acute toxicity category 4 according to Regulation (EC) No 1272/2008.
Executive summary:

The acute oral toxicity of hydrogen peroxide (70 % w/w in aqueous solution) was tested in male and female Crl:CD BR rats receiving 500, 750, 1000, or 1500 mg/kg body weight by oral gavage in compliance with OECD Guideline No. 401. Animals were observed for 14 days and then sacrificed. All animals were subjected to gross necropsy. Additionally, microscopic tissue examinations were performed. Mortality occurred in 2 males receiving 1000 mg/kg, 1 female receiving 500 mg/kg and 2 females receiving 750 mg/kg and in all males and females receiving 1500 mg/kg and most animals were found dead on the day of administration. Compound-related gross changes of the tongue, oesophagus, stomach and duodenum and adhesions in the peritoneal cavity were noted in male and female rats found dead. At all dose levels degenerative ulceration and regenerative hyperplasia of the pyloric antrum of the stomach were found. The ulcerative necrosis penetrated into the gastric epithelium (muscularis mucosa): the severity of the ulcerations was rated minimal to mild.

The LD50 value was 1026 (not confidence interval available) mg/kg for male rats and 693.7 (427 to 960) mg/kg for female rats, respectively.