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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published test report from Nagoya Medical Journal Evaluated data from a reliable secondary source (US-CPSC, 1999; ACGIH, 2005).

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1975
Report date:
1975
Reference Type:
secondary source
Title:
Unnamed
Year:
2000
Reference Type:
secondary source
Title:
Unnamed
Year:
2005
Report date:
2005
Reference Type:
secondary source
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Principles of method if other than guideline:
Rabbits and rats were dosed daily for 20 days with 15%, 20%, or 30% queous solutions of THPC.
Treated animals were continuosly placed under observation even therafter the treatment was discontinued. All animals wer sacrificed after
completion of the experiments and their hematoxylin-eosin stained skin specimens were histological examined.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrakis(hydroxymethyl)phosphonium chloride
EC Number:
204-707-7
EC Name:
Tetrakis(hydroxymethyl)phosphonium chloride
Cas Number:
124-64-1
Molecular formula:
C4H12O4P.Cl
IUPAC Name:
tetrakis(hydroxymethyl)phosphonium chloride

Test animals

Species:
other: rats and rabbits
Sex:
male
Details on test animals or test system and environmental conditions:
88 healthy male white rats of the same strain (bw: 250-300g) were used in a comparative assessment for 7 test items.
30 healthy male white rabbits of the same strain (bw: 3000g) were used in a comparative assessment for 7 test items.

Administration / exposure

Type of coverage:
not specified
Vehicle:
water
Details on exposure:
3 mm portion of the hair from its root was left.
rat: 15%/20%/30% aqueous solutions of THPC (rat: 0.75 ml were applied to 3x3 cm area), corresponding to 450/600/900 mg/kg bw/day (Bittner, CSPC, 1999))
rabbit: 15% and 30% aqueous solutions of THPC (rabbit: 1 ml were applied to 4x4 cm area), corresponding to 50 and 100 mg/kg bw/day (Bittner, CSPC, 1999)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
observation period = treatment period (20 days)
Frequency of treatment:
once a day for 20 consecutive days
No. of animals per sex per dose:
rats: 4 per dose group
rabbits: 2 per dose group
Control animals:
yes, concurrent vehicle
Details on study design:
Protocol amendment: Treatment with THPC were discontinued after day 8 (rats) or after day 6 (rabbit) because of local effects (redness) beginning on day 2 and marked body weight loss. Treated animals were necropsied on day 12 (rats).

Examinations

Observations and examinations performed and frequency:
Rat: Skin reactions beginning on day 2, intensifying till day 6. Falling-off of hair on day 7. The application in rats was discontinued on day 8, but all animals showed marked body weight loss and eventually died on day 9 (high dose group). Surviving animals were necropsied on day 12 (rats).
Rabbit: Redness of skin

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not examined
Details on results:
Rat: Skin reactions beginning on day 2, intensifying till day 6. Falling-off of hair on day 7. The application in rats was discontinued on day 8, but all animals showed marked body weight loss and eventually died on day 9 (high dose group) and were necropsied on day 12 (rats).
Rabbit: Redness of skin on the 2nd day.
Histopathologic findings of the skin: Erythema and epidermal atrophy were observed when rats were treated with 15%, 20%, 30%aqueous THPC (450, 600, 900 mg/kg/day) for 8 days; and all rats of the highest dose group (30% THPC, 900 mg/kg) died after 9 days administration.
When rabbits were treated dermally with a 15% (50 mg/kg/day) THPC solution, severe redness was noted within 6 days; histopathological examination showed subepidermal fibrosis, without the regeneration of papillae, at the 30% concentration (100 mg/kg/day).

Effect levels

open allclose all
Dose descriptor:
LOAEL
Remarks:
rat, local
Effect level:
<= 15 mg/cm² per day
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: severe skin effects at site of contact.
Dose descriptor:
LOAEL
Remarks:
rat, systemic
Effect level:
<= 450 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: marked body weight loss, death of all high dose animals on day 9 (900 mg/kg bw/day)
Dose descriptor:
LOAEL
Remarks:
rabbit, local
Effect level:
<= 17 mg/cm² per day
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: severe skin effects at site of contact
Dose descriptor:
LOAEL
Remarks:
rabbit, systemic
Effect level:
<= 50 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: falling-off of hair, treatment discontinued after day 6

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Low dose groups (15% THPC) showed severe local effects in both rats and rabbits.

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