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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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study review is based on EPA analysis documented "Furfural. Human health Risk assessment for Use on Golf Course Turf (Tees and greens) and Sod Farms

Data source

Reference
Reference Type:
secondary source
Title:
Furfural. Human health Risk assessment for Use on Golf Course Turf (Tees and Greens) and Sod Farms
Author:
EPA
Year:
2010
Bibliographic source:
Office of prevention, Pesticides and Toxic Sustances, United States Environmental Protection Agency

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity 99.4%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
28 days
Frequency of treatment:
6 hours/day, 5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0, 100, 250, 500, 1000, 1000
Basis:
other: mg/kg bw/day
No. of animals per sex per dose:
10

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
no effects observed
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed

Effect levels

open allclose all
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
250 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: adverse clinical signs (males), an increase in motor activity (males) and increased mortality (males and females) at 500 mg/kg/day
Dose descriptor:
NOAEL
Remarks:
local
Effect level:
1 000 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: no indication of dermal irritation at highest dose tested

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

EPA concluded "Due to a high incidence of mortality observed in both the high dose and high dose recovery (1000 mg/kg) groups, the dose level was lowered to 750 mg/kg on Study Day 11; however, the mortality rate remained high and cessation of treatment in this group occurred on Study Day 19. After dosing of the high dose group was terminated, surviving animals from the high dose and high dose recovery group were combined and data were collected by allowing these animals to recover until Study Day 40.

High mortality was also observed in both male and female rats dosed with 500 g/kg/day. Before the 1000/750 mg/kg group was terminated on Study Day 19, four males and twelve females were found dead. In the 500 mg/kg group, one male and two females were found dead on Study Days 17, 19 and 23, respectively, with another male sacrificed moribund on Day 19. Clinical signs observed in males at 500 mg/kg and 1000/750 mg/kg included hypothermia, hypoactivity and hind limb immobility. These effects were not observed in the 500 or 1000/750 mg/kg females or any of the animals in the control, 100 and 250 mg/kg group. No treatment-related effects were observed on body weight, body weight gain, food consumption, food efficiency, hematology, clinical chemistry or urinalysis parameters, and ophthalmoscopic examination. While the functional observational battery (FOB) assessments were comparable between the treated groups and controls, there was a statistically significant increase in motor activity in male rats dosed with 500 mg/kg. Those originally dosed with 1000/750 mg/kg and then allowed to recover did not exhibit increased motor activity when assessed on Study Day 39, indicating a transient effect. No dermal effects associated with treatment were observed in any of the rats.

In the animals found dead or sacrificed moribund, there were hemorrhagic lungs with corresponding lung congestion in 17/20 rats. No other treatment-related findings were identified on gross or histopathological examination."

Applicant's summary and conclusion

Conclusions:
In a 28 day dermal toxicity study a high incidence of mortality was seen at 1000 mg/kg bw/day. Increased mortality, adverse clinical signs and increased motor activity was seen at 500 mg/kg bw/day. The systemic NOAEL is 250 mg/kg bw/day. There was no indication of dermal irritation. The NOAEL for local effects was 1000 mg/kg bw/day.