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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17/09/1987 - 21/04/1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
Chromic acid was administered for 24 hours to the shorn dorsal skin of New Zealand White Rabbits (10/dose level) at 0, 35, 55, 80, 110 or 160 mg/kg bw. Animals were observed for 14 days; bodyweights were recorded weekly. Organ weights were recorded at necrospy.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Chromic acid
EC Number:
231-801-5
EC Name:
Chromic acid
Cas Number:
7738-94-5
Molecular formula:
CrH2O4
IUPAC Name:
dihydroxy(dioxo)chromium
Constituent 2
Chemical structure
Reference substance name:
Chromium trioxide
EC Number:
215-607-8
EC Name:
Chromium trioxide
Cas Number:
1333-82-0
Molecular formula:
CrO3
IUPAC Name:
trioxochromium
Details on test material:
None given

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: King's Wheel Rabbitry, Mount Vernon, Ohio
- Fasting period before study: not specified
- Housing: animals were housed individually in suspended stainless steel cages
- Diet (e.g. ad libitum): animals received Purina® Rabbit Chow HF® (Number 5326), feed was available ad libitum during acclimation and throughout the study
- Water (e.g. ad libitum): Tap water (supplied by the City of Painesville) was available ad libitum through an automatic watering system or water bottles during the acclimation periods and an automatic watering system during the study period
- Acclimation period: animals were housed for a minimun fourteen day acclimation period prior to study initiation
- Method of randomisation in assigning animals to test and control groups: The animals were assigned to the study by a computer-generated random process.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 62° to 70° (A temperature greater than 70°F (73°F) vas recorded once during the acclimation period)
- Humidity (%): 40 to 70% (Relative humidities less than 40% (32 and 34%) were recorded on two days during the acclimation and study periods)
- Air changes (per hr): air flow in the room was equal to eleven or more fresh air changes per hour
- Photoperiod (hrs dark / hrs light): twelve hour light/dark cycle

IN-LIFE DATES: From: February 12, 1988 (animal receipt) To: March 17, 1988 (termination)

Administration / exposure

Type of coverage:
occlusive
Vehicle:
physiological saline
Remarks:
The material was moistened with physiological saline at the time of application to the animal
Details on dermal exposure:
Approximately 24 hours prior to dermal application of the test material, the back and sides of each of the selected rabbits were clipped free of hair with electric clippers. Care was taken to avoid abrading the skin during the clipping of the backs. The dorsal epidermis of each of the animals was considered healthy and suitable for the purpose of the study. For the main study, each animal was identified permanently with an ear tag, imprinted with a unique number, and by cage card. The animals were returned to their cages to await testing on the following day.

For each of the treated groups in the main study, the volume of saline applied to moisten the test material was equivalent to two times the amount of administered test material. A group of control animals received the vehicle (saline) by topical application at a volume equivalent to the dosage of saline administered to animals at the 160 mg/kg level, the highest level tested.
The patch was applied to the site on the back of the rabbit and secured in place with the Blenderm® tape backing. Plastic sheeting (Saran Wrap™, cut approximately 12 inches in length and folded lengthwise in half) was wrapped around the trunk of the animal, covering the patch and tape. To further secure the patch and sheeting, the trunk of the animal was wrapped with elastic Vetrap® which vas secured at either side with 2 inch Blenderm® tape. A plastic restraining collar was placed around the rabbit's neck and the animal was returned to the cage. These procedures were repeated for each animal.
After a twenty-four hour exposure period, the bandaging and patch and the restraining collar were removed from each rabbit. After the removal of each patch, the skin of each back was gently rinsed and wiped, using tap water and disposable paper towels to aid in the removal of any remaining test material.
Duration of exposure:
24 hours
Doses:
0, 35, 55, 80, 110 and 160 mg/kg bw.
No. of animals per sex per dose:
Five animals per sex per dose (expect for 35 mg/kg group: Upon necropsy at the termination of the study, one of the animals assigned to the male group at the 35 mg/kg dose level was found to be a female. Therefore, the 35 mg/kg group consisted of four male and six female rabbits during this study)
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Days -7, -1, 0, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
The gross necropsy included but was not limited to the following examinations:
External: included inspection and palpation of the rabbit, and examination of all external orifices and skin at the exposure site.
Internal: included examination of the tissues in the neck, all major viscera and body cavities. Care was taken to examine the exterior surfaces of the brain and the lining of the cranial cavity as well as the serosal surfaces lining the thoracic, abdominal and pelvic cavities.
The stomach was opened along the greater curvature and the mucosal surface was examined. An eight to ten centimeter segment of the duodenum (nearest to the stomach), jejunum, ileum (nearest to the cecum) and descending colon was opened and was examined.
Tissues considered abnormal were retained in 10% neutral buffered formalin. No histopathology was scheduled.
Organ Weights: For animals surviving to termination (day 14) of the study, the following organs were weighed: brain, heart, lungs with trachea (severed just below the larynx), liver, spleen, each kidney, testes or ovaries.
Statistics:
The acute dermal LD50 with 95% confidence limits (as applicable) was calculated from the mortality data by the probit analysis method of D. J. Finney, Probit Analysis, Cambridge University Press, 1971, for males and females separately and also for the combined sexes. The slope of each dose response curve was calculated and presented as applicable.

Results and discussion

Preliminary study:
Groups of one male and one female rabbit were assigned to each of the following dose groups: 32, 50, 80, 125, 200, 320, 500, 2000 mg/kg. The rabbits were observed for viability at three intervals on the day of dosing and once or twice daily thereafter for at least 7 days. During the viability observations, significant clinical findings were recorded.
The animals in the 200, 320, 500 and 2000 mg/kg groups were found dead within 24 hours of the dose administration. The animals in the 125 mg/kg group were found dead by day 7 following dose administration. Except for mortality, no significant clinical findings were noted in animals in any of the dose groups during the range-finding study. The individual body weights on the day of dose administration ranged from 2450 to 2700 g for male rabbits and from 2300 to 2600 g for female rabbits.
Gross pathologic findings noted externally in animals during the range-finding study included anogenital staining in the 125 to 2000 mg/kg groups and numerous dermal effects at the site of application in each of the groups. The dermal effects included yellow brown staining, hardened and leather-like texture of the skin, thickened skin, sloughing and necrosis. Findings observed internally consisted of pale, mottled and/or swollen kidneys, red foci on the kidneys, a mottled liver and black foci on the luminal surface of the stomach.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
57 mg/kg bw
Based on:
test mat.
95% CL:
>= 47 - <= 66
Mortality:
Deaths occurred at 55 mg/kg bw (3M, 2F); 80 mg/kg bw (5M, 4F); 110 mg/kg bw (5M, 5F) and 160 mg/kg bw (5M, 4F)
Deaths occurred between Days 1-12: The animals which died in the 160 mg/kg group were found dead by day 3 of the study. The animals in the 110 mg/kg group were found dead by day 6. With the exception of one animal in the 80 mg/kg group which was found dead on day 12, the animals which died in the 55 and 80 mg/kg groups were found dead by day 8 of the study
Clinical signs:
other: Signs of systemic toxicity included anogenital staining, nasal discharge, anorexia, hypothermia and prostration. Local findings at the application site included oedema (at early time points), severe erythema and eschar formation. Skin at the application s
Gross pathology:
External findings, noted in rabbits in each of the treated groups were yellow-brown staining of the fur and skin at the application site and areas of dried, thickened, leather-like skin at the application site. Edema and black and/or gray foci were noted at the site of application in animals in the 55 through 160 mg/kg groups. Anogenital staining also was noted in animals in these groups.
Findings observed internally at necropsy in the 55, 80, 110 and 160 mg/kg dose groups were pale and enlarged kidneys and colored (e.g., brown, black or red) foci in the stomach muscosa. Pale kidneys also were observed in the 35 mg/kg group. Yellow discoloration and/or accentuated lobulation of the liver were observed in the 80, 110 and 160 mg/kg groups. These findings were considered treatment related.
No pathologic findings were noted externally in any of the control rabbits. Pathologic findings observed internally in the control animals included multiple red foci on the lungs of one animal, red discoloration of a mandibular lymph node in another animal and a small ovary in a third rabbit.
Other findings:
Potential target organs: kidney
Evaluation of organ weight data showed a possible effect on kidney weights in male and female rabbits. Increases in the mean kidney weights were observed in each of the treated groups when compared with the control group. Increases in kidney weight relative to body and brain weights also were noted in the treated groups when compared with controls. The individual kidney weights of most surviving males and females in the treated groups exceeded the highest individual weights in the control animals.
A possible effect on liver weight was noted only in the one surviving female rabbit in the high dose group. The absolute liver weight and the liver weight relative to brain weight for this animal was less than the liver weights for many females in the other groups. The liver weight relative to body weight for this animal was within the range of control female weights. Interpretation of the significance of the lower liver weight is difficult because there was only one surviving animal in the high dose group.
Organ weight data for each of the other organs in the treated groups were considered similar to control weights.

Any other information on results incl. tables

The acute dermal LD50 of chromic aicd in the rabbit was found to be 57 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
other: Toxic in contact with skin based on EU GHS criteria
Conclusions:
The acute dermal LD50 of chromic acid was found to be 57 mg/kg bw.
Executive summary:

Chromic acid was applied for 24 hours under occlusive conditions to the shorn dorsal skin of New Zealand Whire rabbits (5/sex) at dose levels of 0, 35, 55, 80, 110 or 180 mg/kg bw. Animals were observed for 14 days.

Deaths occurred at dose levels of 55 mg/kg bw/d and greater. Signs of systemic toxicity and local dermal irritation at the application site were observed.

The acute dermal LD50 of chromic acid was found to be 57 mg/kg bw.