Table 15.

Formaldehyde animal carcinogenicity studies.

			Exposure		Tumor rate vs. control (%)	Background tumor rate
Study	Species	Sex	Concentration	Duration	Hematopoietic malignancies	Mean (range)
Inhalation studies
Albert et al., 1982	Rat, Sprague-Dawley	Male	0, 14.7 ppm	6 h/d, 5 d/wk, 19.4 mo	NR (Authors performed complete necropsy and histological sections taken from organs with gross pathological alterations)
As above	As above	Male	As above	As above	NS
Kerns et al., 1983	Rat, Fischer 344	Female	0, 2.0, 5.6, 14.3 ppm	6 h/d, 5 d/wk, 24 mo with follow-up till 30 mo	NS
As above	As above	Male	As above	As above	NS
As above	Mouse, B6C3F1	Female	As above	As above	NS
As above	As above	Male	As above	As above	NS
DeVoney et al., 2006 poster, 2010 poster abstract (analysis of Battelle Columbus Laboratories [1981])*	Rat, Fischer 344	Female	0, 2.0, 5.6, 14.3 ppm	6 h/d, 5 d/wk, 24 mo with follow-up till 30 mo	Leukemia; 24% vs. 15% (14.3 ppm) (no statistical test identified)	Leukemia; 37.3% (24%–54%)†
As above	As above	Male	As above	As above	NS
As above	Mouse, B6C3F1	Female	As above	As above	Lymphoma; 28% vs. 18% (14.3 ppm) (no statistical test identified)	Lymphoma; 19.9% (6%–44%)†
As above	As above	Male	As above	As above	NS
Woutersen, 2007* (analysis of Battelle Columbus Laboratories [1981])	Rat, Fischer 344	Female	0, 2.0, 5.6, 14.3 ppm	6 h/d, 5 d/wk, 24 mo with follow-up till 30 mo	NS
As above	As above	Male	As above	As above	NS
As above	Mouse, B6C3F1	Female	As above	6 h/d, 5 d/wk, 24 mo with follow-up till 27 mo	Lymphoma; considered data immediately after 24-month exposure: 17%, 16%, 9%, 29% (0, 2.0, 5.6, 14.3 ppm, respectively);considered data 3 months after 24-month exposure: 50%, 20%, 15%, 45% (0, 2.0, 5.6, 14.3 ppm, respectively)	Lymphoma; 19.9% (6%–44%)†
As above	As above	Male	As above	As above	NS
Sellakumar et al., 1985 (extended analysis of the study by Albert et al. [1982]).	Rat, Sprague-Dawley	Male	0, 14.8 ppm (with or without ∼10 ppm HCl)	6 h/d, 5 d/wk, >28 mo	NS
Kamata et al., 1997	Rat, Fischer 344	Male	0, 0.3, 2, and 15 ppm	6 h/d, 5 d/wk, 28 mo	NR (No hematological changes were found. Also, the authors examined femur, mesenteric lymph nodes, many other organs, and “any other gross lesions”
Feron et al., 1988	Rat, Wistar	Male	0, 10, 20 ppm	6 h/d, 5 d/wk, (4, 8 or 13 wk); follow-up >28 mo	NR (Animals were autopsied and examined for gross pathological changes. The authors found no gross pathological changes)
Ingestion studies
Til et al., 1989	Rat, Wistar	Female	0, 1.8, 21, 109 mg/kg bw/d (0, 20, 260, 1900 ppm)	Daily, 24 mo, drinking water	NS
As above	Rat, Wistar	Male	0, 1.2, 15, 82 mg/kg bw/d (0, 20, 260, 1900 ppm)	As above	NS
Soffritti et al., 1989	Rat, Sprague-Dawley	Female	Experiment 1: 0, 10, 50, 100, 500, 1000, 1500 (rats were 7 weeks old at start) Experiment 2: 0, 2500 ppm (rats were 25 week old breeder and their offspring)	Daily, 24 mo, drinking water with lifetime follow-up >36 mo	All hematopoietic malignancies Experiment 1: 14% vs. 3% Experiment 2: Breeders: 11.1% vs. 5% Offspring: 0% vs. 6.1%	Up to 19% in males and 14% in males and females combined‡
As above	Rat, Sprague-Dawley	Male	As above	As above	All hematopoietic malignancies Experiment 1: 22% vs. 4%) Experiment 2: Breeders: 11.1% vs. 0% Offspring: 11.1% vs. 5.1%	Up to 19% in males and 14% in males and females combined‡
Tobe et al., 1989	Rat, Wistar	Female	0, 200, 1000, 5000 ppm	Daily, 24 mo, drinking water	NR (No hematological changes were found. Also, authors examined lymph nodes and several other organs and “tumorous tissues”)
As above	As above	Male	As above	As above	As above
Takahashi et al., 1986	Rat, Wistar	Male	0, 5000 ppm	Daily, 32 wk after 8 wk exposure to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), drinking water	NR (Animals were necropsied and “no malignant tumors found outside the gastroduodenal tract”)

Note. NR = not reported; NS = not statistically significant; NA = not applicable/available; mg/kg bw/d = milligram per kilogram body weight per day; ppm = parts per million; wk = week(s); mo = month(s).

^*To adjust for early deaths, Woutersen (2007) used the Peto mortality prevalence trend test, and DeVoney (2006 poster, 2010 poster abstract) “adjusted for early deaths and time to tumor observation.” It should be noted that these two references are a conference presentation and a conference poster, respectively, and are not peer-reviewed publications.

^†Data from Haseman et al. (1998); background tumor rates from NTP studies data based on spontaneous tumor rates in approximately 1000 animals.

^‡Data from the review by Feron et al. (1990) of background leukemia incidence in rats from the same colony used in the study by Soffritti et al. (1989).